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1.
Guerra Martins dos Santos Assunção, José Afonso.
Evolutionary analysis of animal microRNAs.
Degree: PhD, 2013, University of Cambridge
URL: http://www.dspace.cam.ac.uk/handle/1810/244240https://www.repository.cam.ac.uk/bitstream/1810/244240/3/license_url
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https://www.repository.cam.ac.uk/bitstream/1810/244240/9/AfonsoGuerra-PhD-2012-Cambridge.pdf.jpg
► In recent years, microRNAs (miRNAs) have been recognised as important genetic regulators of gene expression in Animals and Plants. They can potentially target a large…
(more)
▼ In recent years, microRNAs (miRNAs) have been recognised as important genetic regulators of gene expression in Animals and Plants. They can potentially target a large fraction of the cellular transcriptome, having been shown to be important for diverse biological processes such as development, cell differentiation, proliferation and metabolism. The publication of the Human genome in 2001 marked the start of a great community effort to sequence a variety of other species. These data have great potential for comparative genomics, that can lead to better biological understanding.
Some miRNA families are known to be highly conserved, across long evolutionary distances, many found in co-transcribed clusters across the genome. While these phenomena have been previously reported, a large-scale analysis of evolutionary patterns was still lacking. Furthermore, the rate at which new relevant data is being made available makes it challenging to keep up and many of the evolutionary studies performed before are now significantly out of date.
This thesis describes a number of approaches taken to analyse miRNA datasets, harnessing the full potential of currently available data for comparative genomics. These were used, not only to revisit many of the notions in the field with a larger and updated dataset, but also to develop novel strategies that enable a coherent view of miRNA evolution at different evolutionary time-scales.
A new tool, described within this thesis, was developed for large-scale, species independent miRNA mapping. An assessment of the evolution of the miRNA reper- toire across species was performed, together with detailed sequence conservation analysis and miRNA family clustering. Phylogenetic profile analysis uncovered in- teresting co-evolution between miRNAs and protein coding genes. The genomic organisation of miRNAs and their conservation across species was also studied, pro- viding detailed conserved synteny maps for miRNAs and proteins across more than 80 species. Finally, at the intra-specific level, I analysed the occurrence of single nucleotide polymorphisms affecting miRNA loci or their predicted target sites.
All the tools built and integrated in this research were made available to the community and designed to be easily updated, making it easier to keep up with the data that is constantly being made available. Many aspects of miRNA biology are still being uncovered, and the ability to easily put these findings into an evolutionary context will potentially be useful for the community.
Subjects/Keywords: Evolution; microRNAs
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APA (6th Edition):
Guerra Martins dos Santos Assunção, J. A. (2013). Evolutionary analysis of animal microRNAs. (Doctoral Dissertation). University of Cambridge. Retrieved from http://www.dspace.cam.ac.uk/handle/1810/244240https://www.repository.cam.ac.uk/bitstream/1810/244240/3/license_url ; https://www.repository.cam.ac.uk/bitstream/1810/244240/4/license_text ; https://www.repository.cam.ac.uk/bitstream/1810/244240/5/license_rdf ; https://www.repository.cam.ac.uk/bitstream/1810/244240/8/AfonsoGuerra-PhD-2012-Cambridge.pdf.txt ; https://www.repository.cam.ac.uk/bitstream/1810/244240/9/AfonsoGuerra-PhD-2012-Cambridge.pdf.jpg
Chicago Manual of Style (16th Edition):
Guerra Martins dos Santos Assunção, José Afonso. “Evolutionary analysis of animal microRNAs.” 2013. Doctoral Dissertation, University of Cambridge. Accessed February 24, 2021.
http://www.dspace.cam.ac.uk/handle/1810/244240https://www.repository.cam.ac.uk/bitstream/1810/244240/3/license_url ; https://www.repository.cam.ac.uk/bitstream/1810/244240/4/license_text ; https://www.repository.cam.ac.uk/bitstream/1810/244240/5/license_rdf ; https://www.repository.cam.ac.uk/bitstream/1810/244240/8/AfonsoGuerra-PhD-2012-Cambridge.pdf.txt ; https://www.repository.cam.ac.uk/bitstream/1810/244240/9/AfonsoGuerra-PhD-2012-Cambridge.pdf.jpg.
MLA Handbook (7th Edition):
Guerra Martins dos Santos Assunção, José Afonso. “Evolutionary analysis of animal microRNAs.” 2013. Web. 24 Feb 2021.
Vancouver:
Guerra Martins dos Santos Assunção JA. Evolutionary analysis of animal microRNAs. [Internet] [Doctoral dissertation]. University of Cambridge; 2013. [cited 2021 Feb 24].
Available from: http://www.dspace.cam.ac.uk/handle/1810/244240https://www.repository.cam.ac.uk/bitstream/1810/244240/3/license_url ; https://www.repository.cam.ac.uk/bitstream/1810/244240/4/license_text ; https://www.repository.cam.ac.uk/bitstream/1810/244240/5/license_rdf ; https://www.repository.cam.ac.uk/bitstream/1810/244240/8/AfonsoGuerra-PhD-2012-Cambridge.pdf.txt ; https://www.repository.cam.ac.uk/bitstream/1810/244240/9/AfonsoGuerra-PhD-2012-Cambridge.pdf.jpg.
Council of Science Editors:
Guerra Martins dos Santos Assunção JA. Evolutionary analysis of animal microRNAs. [Doctoral Dissertation]. University of Cambridge; 2013. Available from: http://www.dspace.cam.ac.uk/handle/1810/244240https://www.repository.cam.ac.uk/bitstream/1810/244240/3/license_url ; https://www.repository.cam.ac.uk/bitstream/1810/244240/4/license_text ; https://www.repository.cam.ac.uk/bitstream/1810/244240/5/license_rdf ; https://www.repository.cam.ac.uk/bitstream/1810/244240/8/AfonsoGuerra-PhD-2012-Cambridge.pdf.txt ; https://www.repository.cam.ac.uk/bitstream/1810/244240/9/AfonsoGuerra-PhD-2012-Cambridge.pdf.jpg
2.
Chen, Chun Jung, Ph. D.
Discovery and function of polyomaviral microRNAs.
Degree: PhD, Biochemistry, 2014, University of Texas – Austin
URL: http://hdl.handle.net/2152/30315
► Polyomaviruses are small, DNA tumor viruses that establish persistent infections in their natural hosts. Several members of the virus family are associated with human pathologies…
(more)
▼ Polyomaviruses are small, DNA tumor viruses that establish persistent infections in their natural hosts. Several members of the virus family are associated with human pathologies such as Progressive Multifocal Leukoencephalopathy (PML), trichodysplasia spinulosa and Merkel cell carcinoma. Polyomaviruses are one of the first virus family known to encode miRNAs. These polyomaviral miRNAs are located antisense to the early transcripts and hence, mediate the autoregulation of the viral early proteins, the T antigens. There are two major questions in the field of polyomaviral miRNAs – What is the biological significance of this miRNA-mediated autoregulation of the early transcripts? Are there other biological significant targets for these polyomaviral miRNAs?
This work addressed these two questions through an evolutionary approach. First, examination of SV40 and JCV variants indicated the high conservation of the miRNAs and their autoregulatory functions. Second, miRNA-mediated autoregulation of the early transcripts is conserved in a newly discovered, evolutionarily divergent viruses, the Bandicoot papillomatosis and Carcinomatosis viruses (BPCVs). Third, by inspecting divergent members of the polyomavirus family, we have shown that some non-human polyomaviruses encode miRNAs, with the function to autoregulate the early transcripts conserved. The conservation of miRNAs both among variants of individual member and across divergent members of the polyomavirus family implies importance. More importantly, a conserved function of autoregulating the early transcript further emphasized the biological relevance of the miRNAs in polyomavirus biology. Yet, the lack of replicative differences between miRNA-expressing and miRNA-null SV40 strains during lytic infections suggests a role for the polyomaviral miRNAs under a different setting, perhaps in the establishment of persistent infection of their natural hosts.
This work represents an evolutionary study of polyomaviral miRNAs that has demonstrated the conserved nature of miRNA-mediated autoregulation of the early transcripts among various members of the polyomavirus and polyoma-like virus families. These results have implicated a potential role for the polyomaviral miRNAs in the establishment of persistent infection and raised the possibility of using the JCV miRNAs as potential biomarkers as a non-invasive form of diagnostic for PML.
Advisors/Committee Members: Sullivan, Christopher S. (advisor).
Subjects/Keywords: MicroRNAs; Polyomavirus
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
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APA (6th Edition):
Chen, Chun Jung, P. D. (2014). Discovery and function of polyomaviral microRNAs. (Doctoral Dissertation). University of Texas – Austin. Retrieved from http://hdl.handle.net/2152/30315
Chicago Manual of Style (16th Edition):
Chen, Chun Jung, Ph D. “Discovery and function of polyomaviral microRNAs.” 2014. Doctoral Dissertation, University of Texas – Austin. Accessed February 24, 2021.
http://hdl.handle.net/2152/30315.
MLA Handbook (7th Edition):
Chen, Chun Jung, Ph D. “Discovery and function of polyomaviral microRNAs.” 2014. Web. 24 Feb 2021.
Vancouver:
Chen, Chun Jung PD. Discovery and function of polyomaviral microRNAs. [Internet] [Doctoral dissertation]. University of Texas – Austin; 2014. [cited 2021 Feb 24].
Available from: http://hdl.handle.net/2152/30315.
Council of Science Editors:
Chen, Chun Jung PD. Discovery and function of polyomaviral microRNAs. [Doctoral Dissertation]. University of Texas – Austin; 2014. Available from: http://hdl.handle.net/2152/30315

Universidade Estadual de Campinas
3.
Lucon, Danielle Ribeiro, 1977-.
Perfil de microRNAs diferencialmente expressos em meduloblastoma e anencefalia: Differential expression profile of microRNA in medulloblastoma and anencephaly.
Degree: 2013, Universidade Estadual de Campinas
URL: http://repositorio.unicamp.br/jspui/handle/REPOSIP/308381
► Abstract: Children with birth defects have a significantly increased risk for developing some type of cancer. Anomalies of central nervous system (CNS) are associated with…
(more)
▼ Abstract: Children with birth defects have a significantly increased risk for developing some type of cancer. Anomalies of central nervous system (CNS) are associated with increased incidence of tumours also from CNS. The comparison between tissue 'anomalous', tumor tissue and normal tissue can help identify genes important in carcinogenesis.
microRNAs (miRNAs) are small non-coding RNA molecules that act negatively on gene expression and play an important role in controlling development, differentiation, apoptosis and cell proliferation. Many miRNAs are expressed in CNS and are known to be dynamically regulated in neurodevelopment. Recently, miRNAs have been associated with CNS tumors and malformations, as meduloblastoma (MB) and anencephaly (AN), respectively. Both tissues are from neuroectodermal and embryonic origins. In this project, we studied the miRNAs differential expressed in tumor tissue of desmoplastic MB of young patients (1-2 years) versus cerebellum and cerebrovascular tissue of fetal with AN versus frontal cortex. The normal tissues were obtained from fetal and newborn autopsy. The gene-metabolic pathways important in carcinogenesis and morphogenesis of miRNAs profile of MB and AN were analyzed in silico. In second chapter, we investigated the MB miRNAs profile that were predominantly downregulated (64/84 miRNAs) and regulates genes involved in development and/or cancer. Most downregulated miRNAs (32/64) were found to belong at the 14q32 locus (14q32 miRNA). Possible mechanisms of 14q32 miRNAs downregulation were investigated by the analysis of publicly available gene expression data sets. The expression of estrogen-related receptor-g (ESRRG), a reported positive transcriptional regulator of some 14q32 miRNAs, was found downregulated in desmoplastic MB. miR-129-5p (11p11.2/7q32.1), miR-206 (6p12.2), and miR-323-3p (14q32.2), were chosen for functional studies in DAOY cells. Overexpression of miR-129-5p using mimics decreased DAOY proliferation. In third chapter we investigated the AN miRNAs profile that were predominantly upregulated (34/52 miRNAs) and regulates genes involved with tube neural defects (DTN) and/or cancer. Between these miRNAs are the miR-21, 34a/c, 182, 500 cluster. miRNAs important in brain development (miR-124, 128, 137, 139) were found downregulated in AN samples. Prospecting for target genes of these miRNAs showed that they play an important role during development and neuronal differentiation. Finally, we compare the miRNAs differential expressed between MB and AN and identified 19 miRNAs in common (underexpression: miR-124, 128, 129 *, 129-5p, 138, 138-1 *, 138-2 *, 139 - 3p, 490-5p, 650, 770-5p; overexpression: miR-199a-3p, 3p-199b, 199a-5p, 21, 214, 214 *, 34a, 574-3p). Most common miRNAs found in MB and AN are known to be involved in cancer and/or are important in brain development. The fact that these miRNAs are deregulated in two different conditions (MB and AN) makes one think that they are functionally relevant in these pathologies. Our results indicate the correlation of…
Advisors/Committee Members: UNIVERSIDADE ESTADUAL DE CAMPINAS (CRUESP), Yunes, José Andrés (advisor), Maurer-Morelli, Cláudia Vianna, 1966- (coadvisor), Cavalcanti, Denise Pontes, 1957- (coadvisor), Universidade Estadual de Campinas. Faculdade de Ciências Médicas (institution), Programa de Pós-Graduação em Ciências Médicas (nameofprogram), Scrideli, Carlos Alberto (committee member), Kobarg, Jörg (committee member), Lopes, Vera Lúcia Gil da Silva (committee member), Lourenço, Gustavo Jacob (committee member).
Subjects/Keywords: MicroRNAs; Meduloblastoma; Anencefalia; MicroRNAs; Medulloblastoma; Anencephaly
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Lucon, Danielle Ribeiro, 1. (2013). Perfil de microRNAs diferencialmente expressos em meduloblastoma e anencefalia: Differential expression profile of microRNA in medulloblastoma and anencephaly. (Thesis). Universidade Estadual de Campinas. Retrieved from http://repositorio.unicamp.br/jspui/handle/REPOSIP/308381
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Lucon, Danielle Ribeiro, 1977-. “Perfil de microRNAs diferencialmente expressos em meduloblastoma e anencefalia: Differential expression profile of microRNA in medulloblastoma and anencephaly.” 2013. Thesis, Universidade Estadual de Campinas. Accessed February 24, 2021.
http://repositorio.unicamp.br/jspui/handle/REPOSIP/308381.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Lucon, Danielle Ribeiro, 1977-. “Perfil de microRNAs diferencialmente expressos em meduloblastoma e anencefalia: Differential expression profile of microRNA in medulloblastoma and anencephaly.” 2013. Web. 24 Feb 2021.
Vancouver:
Lucon, Danielle Ribeiro 1. Perfil de microRNAs diferencialmente expressos em meduloblastoma e anencefalia: Differential expression profile of microRNA in medulloblastoma and anencephaly. [Internet] [Thesis]. Universidade Estadual de Campinas; 2013. [cited 2021 Feb 24].
Available from: http://repositorio.unicamp.br/jspui/handle/REPOSIP/308381.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Lucon, Danielle Ribeiro 1. Perfil de microRNAs diferencialmente expressos em meduloblastoma e anencefalia: Differential expression profile of microRNA in medulloblastoma and anencephaly. [Thesis]. Universidade Estadual de Campinas; 2013. Available from: http://repositorio.unicamp.br/jspui/handle/REPOSIP/308381
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Universidade do Rio Grande do Sul
4.
Beserra, Bárbara Alemar.
MicroRNAs em adenocarcinoma ductal pancreático : novos biomarcadores de diagnóstico e prognóstico.
Degree: 2013, Universidade do Rio Grande do Sul
URL: http://hdl.handle.net/10183/73114
► O adenocarcinoma ductal pancreático (ADP) é uma doença rara, mas possui uma taxa de incidência muito próxima à taxa de letalidade. Parte da alta mortalidade…
(more)
▼ O adenocarcinoma ductal pancreático (ADP) é uma doença rara, mas possui uma taxa de incidência muito próxima à taxa de letalidade. Parte da alta mortalidade do ADP se deve ao diagnóstico difícil (muitas vezes somente possível com análise de tecido pancreático) e tardio da doença, que geralmente acontece com o tumor já em estágio avançado. Assim, a descoberta de biomarcadores não-invasivos surge como uma possibilidade de diagnóstico mais seguro e, de preferência, precoce. Recentemente descobriuse que os microRNAS (miRNAs - pequenos RNAs não-codificantes, envolvidos na iniciação e na manutenção de tumores, incluindo o ADP) são estáveis em amostras circulantes, e a diferença em seus níveis de expressão pode discriminar com acurácia a presença ou ausência de determinadas doenças. Neste estudo, nós avaliamos a expressão de seis miRNAs (miR-21, -34a, -155, -196a, -200b e -376a) escolhidos de acordo com dados prévios da literatura, em amostras de soro e saliva de pacientes com e sem ADP, e também em tecido tumoral e não-tumoral de pacientes com ADP. Esta avaliação comparativa teve como objetivo verificar a presença de biomarcadores de diagnóstico, e possivelmente de prognóstico, neste perfil. Os níveis de expressão foram mensurados através de quantificação relativa, por PCR quantitativo em tempo real. Embora os níveis de expressão tenham se mostrado elevados em todas as amostras de tecido tumoral em relação ao tecido não-tumoral, esta diferença não foi significativa. Isso pode ser explicado pelo pequeno tamanho amostral, pela heterogeneidade tumoral e tecidual e pela ampla variabilidade de expressão dos miRNAs. Em amostras de soro, miR-21 e miR-34a foram significativamente mais expressos em pacientes com ADP e ambos foram capazes de discriminar pacientes com e sem doença com sensibilidade e especificidades clinicamente aceitáveis. Nosso estudo mostrou ainda que existe uma correlação forte e positiva entre os níveis de expressão destes dois miRNAs em amostras de soro e tecido, embora o mecanismo responsável por esta correlação seja desconhecido. A ausência de correlação de miR-21 e de miR-34a, quando analisados individualmente em amostras de soro e tecido pareadas, sugere que diferentes mecanismos regulam a expressão destes miRNAs em diferentes tecidos. Nas amostras de saliva, de modo geral, os níveis de miRNA foram muito baixos, e mesmo os miRNA detectáveis não apresentaram valores de expressão significativamente diferentes entre casos e controles. Tais achados sugerem que os miRNAs escolhidos neste estudo não são biomarcadores salivares adequados para diagnóstico, embora seja necessário uma confirmação destes dados em uma série maior de casos.
Pancreatic ductal adenocarcinoma (PDAC) is a rare disease, whose incidence rates are very close to mortality rates. Part of the high mortality of PDAC is due to its difficult (often only possible with pancreatic tissue analysis) and late diagnosis, when disease is at an advanced stage. Thus, the discovery of noninvasive diagnostic biomarkers emerges as a possibility to perform a…
Advisors/Committee Members: Prolla, Patrícia Ashton.
Subjects/Keywords: Adenocarcinoma; Biomarcadores; MicroRNAs
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Beserra, B. A. (2013). MicroRNAs em adenocarcinoma ductal pancreático : novos biomarcadores de diagnóstico e prognóstico. (Thesis). Universidade do Rio Grande do Sul. Retrieved from http://hdl.handle.net/10183/73114
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Beserra, Bárbara Alemar. “MicroRNAs em adenocarcinoma ductal pancreático : novos biomarcadores de diagnóstico e prognóstico.” 2013. Thesis, Universidade do Rio Grande do Sul. Accessed February 24, 2021.
http://hdl.handle.net/10183/73114.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Beserra, Bárbara Alemar. “MicroRNAs em adenocarcinoma ductal pancreático : novos biomarcadores de diagnóstico e prognóstico.” 2013. Web. 24 Feb 2021.
Vancouver:
Beserra BA. MicroRNAs em adenocarcinoma ductal pancreático : novos biomarcadores de diagnóstico e prognóstico. [Internet] [Thesis]. Universidade do Rio Grande do Sul; 2013. [cited 2021 Feb 24].
Available from: http://hdl.handle.net/10183/73114.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Beserra BA. MicroRNAs em adenocarcinoma ductal pancreático : novos biomarcadores de diagnóstico e prognóstico. [Thesis]. Universidade do Rio Grande do Sul; 2013. Available from: http://hdl.handle.net/10183/73114
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Universidade do Rio Grande do Sul
5.
Vieira, Igor Araújo.
Caracterização das sequências regulatórias de poliadenilação e modulação da expressão por micrornas em um conjunto abrangente de genes de predisposição ao câncer.
Degree: 2017, Universidade do Rio Grande do Sul
URL: http://hdl.handle.net/10183/180496
► A poliadenilação consiste na etapa de processamento da extremidade 3’ dos pré-mRNAs em eucariotos. Duas sequências regulatórias localizadas na região 3’ não-traduzida (3’UTR) desses transcritos…
(more)
▼ A poliadenilação consiste na etapa de processamento da extremidade 3’ dos pré-mRNAs em eucariotos. Duas sequências regulatórias localizadas na região 3’ não-traduzida (3’UTR) desses transcritos primários apresentam um papel fundamental nesse processo: o sinal de poliadenilação (SP) AAUAAA e suas variantes funcionais; e o sítio de clivagem (SC), preferencialmente um dinucleotídeo “CA”. Outros elementos de sequência também situados na região 3’UTR são os sítios de ligação para microRNAs (miRNAs), os quais representam uma classe de pequenos RNAs não-codificantes que regulam negativamente a expressão gênica e podem atuar como supressores de tumor e/ou oncogenes. Os principais objetivos desse estudo foram: (1) caracterizar os SP e SC em um conjunto de genes de predisposição ao câncer (GPC); (2) avaliar a frequência de poliadenilação alternativa entre os GPC estudados; e (3) identificar miRNAs e/ou famílias de miRNAs potencialmente oncogênicos e supressores de tumor considerando o mesmo grupo de genes. Para caracterizar essas sequências nos GPC selecionados (n=117) foram utilizados os bancos de dados do NCBI (referência) e os bancos de dados de poliadenilação alternativa APADB e APASdb. A busca por miRNAs reguladores de genes supressores de tumor (n=81) e oncogenes (n=17) foi realizada utilizando fontes de dados preditos computacionalmente e com validação experimental. Em relação ao objetivo (1), 21 dos 117 GPC (~18%) não apresentaram SP indicados no NCBI, sendo que um método computacional foi empregado para detectar SP putativos nesses genes. A maioria dos SP descritos para GPC nesse banco (74,4%) possuía a sequência canônica AAUAAA, enquanto 24,1% continha a variante funcional AUUAAA. Curiosamente, o dinucleotídeo “AA” representou o SC mais frequente dentre os GPC analisados. Além disso, análises relacionadas ao objetivo (2) identificaram evidências de poliadenilação alternativa (mais de um SP funcional) em 105 GPC (~90%), em comparação com uma estimativa anterior de que isso ocorreria em cerca de 50% dos genes humanos, sugerindo uma maior complexidade na regulação da poliadenilação nesses transcritos. Quanto ao objetivo (3), a família de miRNA miR-192 foi significativamente super-representada entre os genes supressores de tumor (P<0,01), o que sugere 10 uma função potencialmente oncogênica. Em contraste, um número maior de famílias de miRNAs foi fortemente associado com a regulação de oncogenes: miR-128, miR-1471, miR-483, miR-3170 e miR-218. Nossos dados fornecem um mapeamento das sequências regulatórias de poliadenilação (SRP) em GPC, o qual pode ser utilizado no desenvolvimento de análises moleculares incluindo esses elementos da região 3’UTR frequentemente negligenciados na rotina de diagnóstico molecular. Ademais, estudos funcionais devem ser realizados para validar as funções potencialmente atribuídas às famílias de miRNAs aqui mencionadas. Em suma, esse é o primeiro estudo focado nesse tipo de caracterização abrangente (SRP e miRNAs) em GPC.
Polyadenylation is the processing step of 3’end in eukaryotic…
Advisors/Committee Members: Prolla, Patrícia Ashton.
Subjects/Keywords: Neoplasias; MicroRNAs; Poliadenilação
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Vieira, I. A. (2017). Caracterização das sequências regulatórias de poliadenilação e modulação da expressão por micrornas em um conjunto abrangente de genes de predisposição ao câncer. (Thesis). Universidade do Rio Grande do Sul. Retrieved from http://hdl.handle.net/10183/180496
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Vieira, Igor Araújo. “Caracterização das sequências regulatórias de poliadenilação e modulação da expressão por micrornas em um conjunto abrangente de genes de predisposição ao câncer.” 2017. Thesis, Universidade do Rio Grande do Sul. Accessed February 24, 2021.
http://hdl.handle.net/10183/180496.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Vieira, Igor Araújo. “Caracterização das sequências regulatórias de poliadenilação e modulação da expressão por micrornas em um conjunto abrangente de genes de predisposição ao câncer.” 2017. Web. 24 Feb 2021.
Vancouver:
Vieira IA. Caracterização das sequências regulatórias de poliadenilação e modulação da expressão por micrornas em um conjunto abrangente de genes de predisposição ao câncer. [Internet] [Thesis]. Universidade do Rio Grande do Sul; 2017. [cited 2021 Feb 24].
Available from: http://hdl.handle.net/10183/180496.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Vieira IA. Caracterização das sequências regulatórias de poliadenilação e modulação da expressão por micrornas em um conjunto abrangente de genes de predisposição ao câncer. [Thesis]. Universidade do Rio Grande do Sul; 2017. Available from: http://hdl.handle.net/10183/180496
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Texas Southwestern Medical Center
6.
Carrer, Michele.
Regulation of Metabolic Processes by Micrornas and Class I Histone Deacetylases.
Degree: 2013, University of Texas Southwestern Medical Center
URL: http://hdl.handle.net/2152.5/1232
► Obesity is a medical condition resulting from accumulation of excess body fat that affects more than 30% of the adult population in the U.S. Obesity-related…
(more)
▼ Obesity is a medical condition resulting from accumulation of excess body fat that affects more than 30% of the adult population in the U.S. Obesity-related pathological conditions include heart disease, stroke, type 2 diabetes and certain types of cancer. Despite the high incidence and the elevated social costs, the molecular basis of obesity and associated metabolic syndrome are still poorly understood. Yet, the need for novel therapeutic approaches for the treatment and prevention of obesity remains. In humans and animal model of disease, hallmarks of obesity include dysregulation of genes involved in mitochondrial function, lipid uptake and lipid storage. The dynamic and modifiable regulation of transcriptional pathways that control mitochondrial function and adipogenesis, as well as additional aspects of mammalian metabolism, will provide new approaches for pharmacological intervention in obesity. Thus, the modulation of epigenetic histone modifications and microRNA functions represents a potentially powerful approach for the treatment of metabolic disorders. We show that the Ppargc1b gene, which encodes the PGC-1β protein, also co-transcribes two
microRNAs, miR-378 and miR-378*. Mice lacking miR-378/378* are resistant to high fat diet-induced obesity and display enhanced mitochondrial fatty acid metabolism and elevated oxidative capacity of insulin-target tissues. Taken together, our findings reveal that miR-378 and miR-378* function as integral components of the regulatory circuit formed by PGC-1beta and nuclear hormone receptors to control the overall oxidative capacity and energy homeostasis of insulin-target tissues. MiR-378/378* mutant mice do not display overt phenotypes under normal laboratory conditions, whereas their phenotypes become apparent under conditions of stress, in this case in response to excessive caloric intake. Thus, pharmacological modulation of miR-378/378* function might represent an effective approach in the treatment of obesity. In obese humans and mice, the unused caloric energy resulting from excessive net caloric intake is converted to triglycerides and stored in adipocytes for further usage. Lipid accumulation within adipocytes is under the control of a cascade of transcription factors that interact with histone acetyltransferases and deacetylases. We show that histone deacetylase inhibitors efficiently block adipocyte differentiation in vitro. Furthermore, through a loss-of-function approach, we provide evidence that histone deacetylases 1 and 2 play redundant and requisite roles in adipogenesis. In conclusion, we unveiled previously unrecognized roles for miR-378/378* in the control of mitochondrial metabolism and energy homeostasis, and for histone deacetylases in the control of adipocyte differentiation.
Advisors/Committee Members: Olson, Eric N..
Subjects/Keywords: Adipocytes; MicroRNAs; Mitochondria
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APA (6th Edition):
Carrer, M. (2013). Regulation of Metabolic Processes by Micrornas and Class I Histone Deacetylases. (Thesis). University of Texas Southwestern Medical Center. Retrieved from http://hdl.handle.net/2152.5/1232
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Carrer, Michele. “Regulation of Metabolic Processes by Micrornas and Class I Histone Deacetylases.” 2013. Thesis, University of Texas Southwestern Medical Center. Accessed February 24, 2021.
http://hdl.handle.net/2152.5/1232.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Carrer, Michele. “Regulation of Metabolic Processes by Micrornas and Class I Histone Deacetylases.” 2013. Web. 24 Feb 2021.
Vancouver:
Carrer M. Regulation of Metabolic Processes by Micrornas and Class I Histone Deacetylases. [Internet] [Thesis]. University of Texas Southwestern Medical Center; 2013. [cited 2021 Feb 24].
Available from: http://hdl.handle.net/2152.5/1232.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Carrer M. Regulation of Metabolic Processes by Micrornas and Class I Histone Deacetylases. [Thesis]. University of Texas Southwestern Medical Center; 2013. Available from: http://hdl.handle.net/2152.5/1232
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Texas Southwestern Medical Center
7.
Johnson, Brett A.
Regulation of Exercise-Dependent Cardiac Growth by MicroRNAs.
Degree: 2013, University of Texas Southwestern Medical Center
URL: http://hdl.handle.net/2152.5/1219
► The heart is an adaptive organ which undergoes pathological or physiological remodeling in response to a variety of stimuli to meet the demands of the…
(more)
▼ The heart is an adaptive organ which undergoes pathological or physiological remodeling in response to a variety of stimuli to meet the demands of the body. Chronic exercise training promotes a physiological remodeling response in which the heart increases in size to match loading demands. In this thesis, I present my studies on the function of
microRNAs during exercise-induced cardiac remodeling.
First, I show the expression of muscle-specific microRNA (miRNA), miR-499, is down-regulated by voluntary free-wheel running in hearts of mice. I hypothesized the reduction of miR-499 may be required for exercise-induced cardiac hypertrophy. I found forced cardiac over-expression of miR-499 was associated with diminished physiological cardiac growth, whereas genetic deletion and antimiR mediated inhibition of miR-499 caused enhanced physiological growth following exercise. I also explored the mechanism by which miR-499 represses exercise-induced cardiac growth. I determined the repressive effects of miR-499 are mediated through regulation of IGF-1/PI-3K/Akt and beta-catenin signaling pathways, which drive physiological growth of the heart. I demonstrated the effects of miR-499 on physiological cardiac growth are mediated, at least in part, through repression of a network of genes including p85-alpha, Rictor, Lin7c and Fzd4. Collectively, the results of my thesis research identify miR-499 as a pivotal regulator of exercise-induced cardiac hypertrophy.
Advisors/Committee Members: Olson, Eric N..
Subjects/Keywords: MicroRNAs; Heart; Exercise
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Johnson, B. A. (2013). Regulation of Exercise-Dependent Cardiac Growth by MicroRNAs. (Thesis). University of Texas Southwestern Medical Center. Retrieved from http://hdl.handle.net/2152.5/1219
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Johnson, Brett A. “Regulation of Exercise-Dependent Cardiac Growth by MicroRNAs.” 2013. Thesis, University of Texas Southwestern Medical Center. Accessed February 24, 2021.
http://hdl.handle.net/2152.5/1219.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Johnson, Brett A. “Regulation of Exercise-Dependent Cardiac Growth by MicroRNAs.” 2013. Web. 24 Feb 2021.
Vancouver:
Johnson BA. Regulation of Exercise-Dependent Cardiac Growth by MicroRNAs. [Internet] [Thesis]. University of Texas Southwestern Medical Center; 2013. [cited 2021 Feb 24].
Available from: http://hdl.handle.net/2152.5/1219.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Johnson BA. Regulation of Exercise-Dependent Cardiac Growth by MicroRNAs. [Thesis]. University of Texas Southwestern Medical Center; 2013. Available from: http://hdl.handle.net/2152.5/1219
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Illinois – Chicago
8.
Seal, Alexandra A.
Viral MicroRNAs Modulate Transcriptome in Oral Keratinocytes and Alter Cytokine Levels in Myeloid Cells.
Degree: 2017, University of Illinois – Chicago
URL: http://hdl.handle.net/10027/21736
► MicroRNAs (miRNAs) are small, non-coding RNAs of ~18-25 nucleotides that have gained extensive attention as critical regulators in complex gene networks. Some of the key…
(more)
▼ MicroRNAs (miRNAs) are small, non-coding RNAs of ~18-25 nucleotides that have gained extensive attention as critical regulators in complex gene networks. Some of the key regulations involve immune cell lineage commitment, differentiation, maturation, and maintenance of immune homeostasis and function. Many viruses encode miRNAs that directly modulate expression of genes of the innate immune system, which includes proteins involved in promoting apoptosis and recruitment of cells of the immune system. In this study, we examined the expression profiles of three known v-miRNAs (vmiRs) from HSV-1 (miR-H1), KSHV (miR-K12-3), and HCMV (miR-US4) in healthy and diseased periodontal tissues from non-obese and obese subjects and observed increased levels of these vmiRs in diseased tissues compared to respective controls. Next, we investigated the impact of miR-H1 and miR-K12-3 overexpression on the host transcriptome focusing on gingival epithelial cells that are target sites for various HHVs. Expression of more than 1300 genes were altered in human oral keratinocytes (HOK) transfected with miR-H1 and miR-K12-3. Global pathway analysis identified dysregulation of key signaling genes and pathways that may favor virus persistence. Using bioinformatic analysis, we identified hundreds of potential vmiR binding sites on genes downregualted by miR-H1 and miR-K12-3 suggesting direct regualtion of these genes by vmiRs. We also assessed the expression of six selected vmiR-deregulated genes in myeloid inflammtory cells viz., macrophages and dendritic cells. Our results show that three genes exhibit similar changes in myeloid cells as observed in HOK while the remaining genes exhibit cell specific changes.
Finally, cytokine responses of vmiR expressing myeloid cells challenged with lipopolysacchride (LPS) derived from the periodontal pathogen, Aggregatibacter actinomycetemcomitans (Aa) show increased levels of TNF-α but reduced IL-12p40 indicating immunomoduatory functions of vmiRs. Overall, our resutls demonstrate clinical and functional relevance of pathogenic viral molecules viz., vmiRs capable of modulating expression of key gene and pathways in HOK and cytokine expression in myeloid cells which may favor an environment condusive to periodontal pathology.
Advisors/Committee Members: Nares, Salvador (advisor), Atsawasuwam, Phimon (committee member), Luan, Xianghong (committee member), Zhou, Xiaofeng (committee member), Naqvi, Afsar (committee member), Nares, Salvador (chair).
Subjects/Keywords: MiRNAs; MicroRNAs; VmiRNAs
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Seal, A. A. (2017). Viral MicroRNAs Modulate Transcriptome in Oral Keratinocytes and Alter Cytokine Levels in Myeloid Cells. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/21736
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Seal, Alexandra A. “Viral MicroRNAs Modulate Transcriptome in Oral Keratinocytes and Alter Cytokine Levels in Myeloid Cells.” 2017. Thesis, University of Illinois – Chicago. Accessed February 24, 2021.
http://hdl.handle.net/10027/21736.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Seal, Alexandra A. “Viral MicroRNAs Modulate Transcriptome in Oral Keratinocytes and Alter Cytokine Levels in Myeloid Cells.” 2017. Web. 24 Feb 2021.
Vancouver:
Seal AA. Viral MicroRNAs Modulate Transcriptome in Oral Keratinocytes and Alter Cytokine Levels in Myeloid Cells. [Internet] [Thesis]. University of Illinois – Chicago; 2017. [cited 2021 Feb 24].
Available from: http://hdl.handle.net/10027/21736.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Seal AA. Viral MicroRNAs Modulate Transcriptome in Oral Keratinocytes and Alter Cytokine Levels in Myeloid Cells. [Thesis]. University of Illinois – Chicago; 2017. Available from: http://hdl.handle.net/10027/21736
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Melbourne
9.
Narayan, Nisha.
The role of microRNAs miR-155 and miR-211 in myeloid malignancies.
Degree: 2016, University of Melbourne
URL: http://hdl.handle.net/11343/123488
► MicroRNAs are a class of non-coding RNA molecules that post-transcriptionally regulate several critical cellular processes including cell survival, proliferation and differentiation. A subset of microRNAs…
(more)
▼ MicroRNAs are a class of non-coding RNA molecules that post-transcriptionally regulate several critical cellular processes including cell survival, proliferation and differentiation. A subset of microRNAs has well-established roles in cancer development, and microRNAs are emerging as important biomarkers of disease and potential therapeutic targets. This thesis focuses on the role of two microRNAs, miR-155 and miR-211 in myeloid malignancies, particularly in AML.
miR-155 is a well-recognized oncomiR in B cell lymphoma. The role of miR-155 in AML, however, is rather enigmatic. Contrasting data suggest miR-155 can block differentiation and promote proliferation, and so function like an oncogene, or it may repress proliferation, induce apoptosis and promote differentiation, functions more closely aligned with tumour suppressor function. To establish if miR-155 is an oncogene or tumour suppressor in AML, the effects of enforced miR-155 expression were studied in murine models of AML, in vitro and in vivo. I show that enforced expression of miR-155 to the highest levels, suppresses colony formation and cell proliferation of AML cells in vitro, and is selected against in tumours in vitro and in vivo. Over time, however, AML cells are selected for intermediate levels of miR-155 expression, which is associated with restored colony formation and increased tumour burden in vivo. Additionally, I show that the differential effects of intermediate and high miR-155 expression levels in AML result from targeting contrasting transcriptional networks in AML. Importantly, I show that the dose-dependent associations of miR-155 expression and phenotype extends to pediatric AML, where the elevated miR-155 levels expressed in patients correlates to the intermediate and not the high miR-155 expression levels, detected in mouse tumours.
miR-211 is a microRNA of which very little is known, and is primarily associated with invasion and metastasis in melanoma. In a screen of 700 microRNAs in an inducible model of myeloid differentiation, miR-211 was one of the most highly differentially expressed microRNAs, suggesting that it may have a role in the regulation of myeloid differentiation and consequently in myeloid leukemia. In this thesis, using a system of enforced miR-211 expression in hematopoietic reconstitution experiments, I describe for the first time a novel role for miR-211 as an oncogene in AML. I show that miR-211 drives a partially penetrant myeloid disease characterized by an expansion of CD11b/Gr-1 myeloid cells, anemia, thrombocytopenia and infiltration of peripheral hematopoietic tissues, phenotypically resembling myeloid leukemia. Additionally, I show that miR-211 expression is elevated in a subset of pediatric AML patients, and present data describing the molecular actions of miR-211 in the disease.
Subjects/Keywords: microRNAs; leukemia; AML
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Narayan, N. (2016). The role of microRNAs miR-155 and miR-211 in myeloid malignancies. (Doctoral Dissertation). University of Melbourne. Retrieved from http://hdl.handle.net/11343/123488
Chicago Manual of Style (16th Edition):
Narayan, Nisha. “The role of microRNAs miR-155 and miR-211 in myeloid malignancies.” 2016. Doctoral Dissertation, University of Melbourne. Accessed February 24, 2021.
http://hdl.handle.net/11343/123488.
MLA Handbook (7th Edition):
Narayan, Nisha. “The role of microRNAs miR-155 and miR-211 in myeloid malignancies.” 2016. Web. 24 Feb 2021.
Vancouver:
Narayan N. The role of microRNAs miR-155 and miR-211 in myeloid malignancies. [Internet] [Doctoral dissertation]. University of Melbourne; 2016. [cited 2021 Feb 24].
Available from: http://hdl.handle.net/11343/123488.
Council of Science Editors:
Narayan N. The role of microRNAs miR-155 and miR-211 in myeloid malignancies. [Doctoral Dissertation]. University of Melbourne; 2016. Available from: http://hdl.handle.net/11343/123488

University of Cambridge
10.
Guerra Martins dos Santos Assunção, José Afonso.
Evolutionary analysis of animal microRNAs.
Degree: PhD, 2013, University of Cambridge
URL: https://doi.org/10.17863/CAM.15983
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.566199
► In recent years, microRNAs (miRNAs) have been recognised as important genetic regulators of gene expression in Animals and Plants. They can potentially target a large…
(more)
▼ In recent years, microRNAs (miRNAs) have been recognised as important genetic regulators of gene expression in Animals and Plants. They can potentially target a large fraction of the cellular transcriptome, having been shown to be important for diverse biological processes such as development, cell differentiation, proliferation and metabolism. The publication of the Human genome in 2001 marked the start of a great community effort to sequence a variety of other species. These data have great potential for comparative genomics, that can lead to better biological understanding. Some miRNA families are known to be highly conserved, across long evolutionary distances, many found in co-transcribed clusters across the genome. While these phenomena have been previously reported, a large-scale analysis of evolutionary patterns was still lacking. Furthermore, the rate at which new relevant data is being made available makes it challenging to keep up and many of the evolutionary studies performed before are now significantly out of date. This thesis describes a number of approaches taken to analyse miRNA datasets, harnessing the full potential of currently available data for comparative genomics. These were used, not only to revisit many of the notions in the field with a larger and updated dataset, but also to develop novel strategies that enable a coherent view of miRNA evolution at different evolutionary time-scales. A new tool, described within this thesis, was developed for large-scale, species independent miRNA mapping. An assessment of the evolution of the miRNA reper- toire across species was performed, together with detailed sequence conservation analysis and miRNA family clustering. Phylogenetic profile analysis uncovered in- teresting co-evolution between miRNAs and protein coding genes. The genomic organisation of miRNAs and their conservation across species was also studied, pro- viding detailed conserved synteny maps for miRNAs and proteins across more than 80 species. Finally, at the intra-specific level, I analysed the occurrence of single nucleotide polymorphisms affecting miRNA loci or their predicted target sites. All the tools built and integrated in this research were made available to the community and designed to be easily updated, making it easier to keep up with the data that is constantly being made available. Many aspects of miRNA biology are still being uncovered, and the ability to easily put these findings into an evolutionary context will potentially be useful for the community.
Subjects/Keywords: 570.285; Evolution; microRNAs
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Guerra Martins dos Santos Assunção, J. A. (2013). Evolutionary analysis of animal microRNAs. (Doctoral Dissertation). University of Cambridge. Retrieved from https://doi.org/10.17863/CAM.15983 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.566199
Chicago Manual of Style (16th Edition):
Guerra Martins dos Santos Assunção, José Afonso. “Evolutionary analysis of animal microRNAs.” 2013. Doctoral Dissertation, University of Cambridge. Accessed February 24, 2021.
https://doi.org/10.17863/CAM.15983 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.566199.
MLA Handbook (7th Edition):
Guerra Martins dos Santos Assunção, José Afonso. “Evolutionary analysis of animal microRNAs.” 2013. Web. 24 Feb 2021.
Vancouver:
Guerra Martins dos Santos Assunção JA. Evolutionary analysis of animal microRNAs. [Internet] [Doctoral dissertation]. University of Cambridge; 2013. [cited 2021 Feb 24].
Available from: https://doi.org/10.17863/CAM.15983 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.566199.
Council of Science Editors:
Guerra Martins dos Santos Assunção JA. Evolutionary analysis of animal microRNAs. [Doctoral Dissertation]. University of Cambridge; 2013. Available from: https://doi.org/10.17863/CAM.15983 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.566199

Universidade do Rio Grande do Sul
11.
Morais, Guilherme Loss de.
MicroRNAs de sementes de soja maduras e em germinação e Transfer RNA- derived Fragments (tRFs) associados a proteínas argonautas de Arabidopsis.
Degree: 2013, Universidade do Rio Grande do Sul
URL: http://hdl.handle.net/10183/78085
► O advento de técnicas de sequenciamento de alta eficiência possibilitou o estudo mais aprofundado de pequenos RNAs, como os microRNAs (miRNAs), a classe melhor caracterizada,…
(more)
▼ O advento de técnicas de sequenciamento de alta eficiência possibilitou o estudo mais aprofundado de pequenos RNAs, como os microRNAs (miRNAs), a classe melhor caracterizada, e a identificação de novas classes como a dos transfer RNA-derived Fragments (tRFs). Os pequenos RNAs podem atuar como reguladores negativos da expressão gênica do seu transcrito alvo. Este mecanismo, denominado Silenciamento Gênico Pós-Transcricional (PTGS) ou RNA interferência (RNAi), pode ocorrer pela indução da clivagem do transcrito alvo, ou pela repressão da tradução do mesmo. Em soja, ainda não foram descritos miRNAs atuantes na germinação da semente, os quais foram abordados no primeiro capítulo desta tese. Utilizando duas bibliotecas de sequenciamento de alta eficiência, uma relativa a sementes maduras e outra composta de uma combinação de sementes em germinação (3, 5 e 7 dias), foram identificados um total de 178 microRNAs, sendo 36 inéditos. Dos 178, 8 miRNAs com alvos potencialmente relacionados à germinação da semente, às rotas de auxina, giberelina, metabolismo lipídico, de nitrogênio e homeostase de potencial redox, foram validados por análise de degradoma. O segundo capítulo aborda a caracterização de tRFs em Arabidopsis associados com proteínas Argonauta (AGO), as quais são essenciais ao RNAi. Foram utilizadas 26 bibliotecas de sequenciamento de argonautas imunoprecipitadas (AGO-IP), relativas às AGOs 1, 2, 4, 5, 7 e 9, além de 3 bibliotecas de degradoma. O mapeamento destas sequências nos tRNAs de Arabidopsis revelou que estes pequenos RNAs são majoritariamente associados a AGO1 e 2, sendo a classe 5' de 19 nucleotídeos de comprimento a mais comum. Contudo, estes não obedecem aos critérios de direcionamento a proteínas AGO relativos ao primeiro nucleotídeo do pequeno RNA, como ocorre com miRNAs. Foram identificados quatro transcritos alvos, validados por análise do degradoma, os quais possivelmente sofrem PTGS via tRFs. Ambos os capítulos apresentam uma robusta caracterização in silico de pequenos RNAs em plantas inferindo suas possíveis funções. Contudo, mais experimentos devem ser efetuados para confirmação de seus papeis em soja e Arabidopsis.
The advent of the deep sequencing approach enabled a better characterization of small RNAs, such as microRNAs (miRNAs), the well-known small RNA class, and the identification of new classes like the transfer RNA-derived Fragments (tRFs). The small RNAs can act as negative regulators of gene expression of their target transcript. This mechanism, known as Post Transcriptional Gene Silencing (PTGS), involves dicing of the target transcript, or translational repression. In soybean, the microRNAs acting on seed germination are unknown. These miRNAs were described in the first chapter of this thesis. Using two deep sequencing libraries, relative to the mature seeds and a combination of germinating seeds (3, 5 and 7 days). A total of 178 miRNAs were identified, including 36 new ones. Eight miRNAs had targets potentially related to seed germination including some acting on auxin and…
Advisors/Committee Members: Margis, Rogerio.
Subjects/Keywords: MicroRNAs; Soja; Arabidopsis thaliana
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Morais, G. L. d. (2013). MicroRNAs de sementes de soja maduras e em germinação e Transfer RNA- derived Fragments (tRFs) associados a proteínas argonautas de Arabidopsis. (Thesis). Universidade do Rio Grande do Sul. Retrieved from http://hdl.handle.net/10183/78085
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Morais, Guilherme Loss de. “MicroRNAs de sementes de soja maduras e em germinação e Transfer RNA- derived Fragments (tRFs) associados a proteínas argonautas de Arabidopsis.” 2013. Thesis, Universidade do Rio Grande do Sul. Accessed February 24, 2021.
http://hdl.handle.net/10183/78085.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Morais, Guilherme Loss de. “MicroRNAs de sementes de soja maduras e em germinação e Transfer RNA- derived Fragments (tRFs) associados a proteínas argonautas de Arabidopsis.” 2013. Web. 24 Feb 2021.
Vancouver:
Morais GLd. MicroRNAs de sementes de soja maduras e em germinação e Transfer RNA- derived Fragments (tRFs) associados a proteínas argonautas de Arabidopsis. [Internet] [Thesis]. Universidade do Rio Grande do Sul; 2013. [cited 2021 Feb 24].
Available from: http://hdl.handle.net/10183/78085.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Morais GLd. MicroRNAs de sementes de soja maduras e em germinação e Transfer RNA- derived Fragments (tRFs) associados a proteínas argonautas de Arabidopsis. [Thesis]. Universidade do Rio Grande do Sul; 2013. Available from: http://hdl.handle.net/10183/78085
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Universidade do Rio Grande do Sul
12.
Machado, Ronei Dorneles.
Análise da expressão de miRNAS durante o desenvolvimento de sementes de BRASSICA NAPUS e predição de seus possíveis genes alvos.
Degree: 2013, Universidade do Rio Grande do Sul
URL: http://hdl.handle.net/10183/90466
► Brassica napus (canola) é a terceira cultura oleaginosa mais produzida no mundo, fornecendo cerca de 13% de toda a oferta mundial de óleo vegetal. Durante…
(more)
▼ Brassica napus (canola) é a terceira cultura oleaginosa mais produzida no mundo, fornecendo cerca de 13% de toda a oferta mundial de óleo vegetal. Durante o desenvolvimento de sementes, B. napus acumula compostos de reservas em estádios e tecidos específicos. A maioria destes compostos de reservas são lípidos (30-40%) e proteínas (17-26%), sendo quase que exclusivamente armazenados nos cotilédones do embrião maduro. Os microRNAs (miRNAs) desempenham um papel essencial em diversos aspectos do desenvolvimento de sementes. A função destes pequenos RNAs (sRNAs) endógenos não-codificantes é regular a expressão gênica, principalmente através da clivagem e a inibição de tradução de mRNA alvo. Estudos recentes têm contribuído para a identificação de miRNAs em sementes de B. napus, mas a expressão temporal e as funções regulatórias dos miRNAs em sementes de B. napus, especialmente durante a maturação, são desconhecidas. Para entender os padrões de expressão temporal dos miRNAs durante o desenvolvimento de sementes por RT-qPCR, este trabalho se concentra primeiramente na determinação de genes de referência para serem utilizados como normalizadores em estudos de RT-qPCR e no perfil de expressão dos miRNAs durante o desenvolvimento de sementes. A estabilidade da expressão de 16 mRNA e 43 miRNAs de B. napus foi avaliada em amostras de folha, tecidos florais e diferentes estágios de desenvolvimento de sementes. Nossas análises demonstraram que os miRNAs apresentam uma maior estabilidade de expressão do que genes que codificam proteínas, e a combinação miR156-7, miR11-1 e miR408-1 foi a mais apropriada para ser utilizada como normalizadores em estudos de expressão gênica por RT-qPCR. O perfil de expressão de 40 miRNAs foi avaliado ao longo do desenvolvimento de sementes. A maioria dos miRNAs teve sua expressão induzida durante a maturação de sementes, enquanto um pequeno número foi preferencialmente expressos em estágios iniciais do desenvolvimento das sementes. Um miRNA inédito, denominado miR03-1, apresentou uma expressão diferencial entre os estágios precoces e tardios do desenvolvimento. A expressão do miR03-1 é fortemente induzida 21 dias após o florescimento. A partir de uma abordagem computacional para predição de possíveis genes-alvo de miRNAs de B. napus foi possível identificar um total de 481 alvos putativos para 104 sequências maduras de miRNAs. Todos os alvos preditos estão diretamente relacionados com o metabolismo lipídico, dentre estes fatores de transcrição e enzimas-chave do metabolismo lipídico. O estudo da regulação destes genes por miRNAs em diferentes estágios do desenvolvimento de semente contribuirá para o entendimento dos mecanismos moleculares envolvidos no metabolismo lipidico.
Brassica napus (canola) is the third largest oilseed crop in the world, providing approximately 13% of the world's supply of vegetable oil. During seed development, B. napus build up storage reserves in specific stages and tissues. The vast majority of these reserves are made up of lipids (30–40%) and proteins (17–26%) that are…
Advisors/Committee Members: Margis-Pinheiro, Márcia.
Subjects/Keywords: Brassica napus; MicroRNAs; Semente
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Machado, R. D. (2013). Análise da expressão de miRNAS durante o desenvolvimento de sementes de BRASSICA NAPUS e predição de seus possíveis genes alvos. (Thesis). Universidade do Rio Grande do Sul. Retrieved from http://hdl.handle.net/10183/90466
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Machado, Ronei Dorneles. “Análise da expressão de miRNAS durante o desenvolvimento de sementes de BRASSICA NAPUS e predição de seus possíveis genes alvos.” 2013. Thesis, Universidade do Rio Grande do Sul. Accessed February 24, 2021.
http://hdl.handle.net/10183/90466.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Machado, Ronei Dorneles. “Análise da expressão de miRNAS durante o desenvolvimento de sementes de BRASSICA NAPUS e predição de seus possíveis genes alvos.” 2013. Web. 24 Feb 2021.
Vancouver:
Machado RD. Análise da expressão de miRNAS durante o desenvolvimento de sementes de BRASSICA NAPUS e predição de seus possíveis genes alvos. [Internet] [Thesis]. Universidade do Rio Grande do Sul; 2013. [cited 2021 Feb 24].
Available from: http://hdl.handle.net/10183/90466.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Machado RD. Análise da expressão de miRNAS durante o desenvolvimento de sementes de BRASSICA NAPUS e predição de seus possíveis genes alvos. [Thesis]. Universidade do Rio Grande do Sul; 2013. Available from: http://hdl.handle.net/10183/90466
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Universidade do Rio Grande do Sul
13.
Ribeiro, Patrícia Lisbôa Izetti.
Biomarcadores e novas terapias no diagnóstico e tratamento do adenocarcinoma ductal pancreático : estudos de expressão gênica e resposta celular.
Degree: 2014, Universidade do Rio Grande do Sul
URL: http://hdl.handle.net/10183/117905
► O adenocarcinoma ductal pancreático é uma neoplasia cuja incidência é quase igual à mortalidade. Os principais fatores que contribuem para a baixa sobrevida no câncer…
(more)
▼ O adenocarcinoma ductal pancreático é uma neoplasia cuja incidência é quase igual à mortalidade. Os principais fatores que contribuem para a baixa sobrevida no câncer de pâncreas incluem a sua biologia tumoral agressiva, o diagnóstico tardio e a baixa eficácia dos tratamentos atualmente disponíveis. Com o presente estudo, objetivamos identificar biomarcadores com potencial diagnóstico, bem como novas terapias que possam contribuir para o controle do câncer de pâncreas. Para isso, foram propostas duas diferentes linhas de investigação: o estudo de biomarcadores salivares como possíveis ferramentas para a detecção do câncer de pâncreas e a avaliação de novas drogas (isoladas e em combinação) em linhagens de adenocarcinoma ductal pancreático. Dessa forma, os objetivos específicos desse trabalho foram: 1) estudar a expressão dos genes KRAS e DPM1 na saliva de pacientes com adenocarcinoma ductal pancreático, pancreatite crônica e controles sem doença pancreática; 2) avaliar a reativação farmacológica da proteína p53 mutante pelo composto PRIMA-1 em linhagens tumorais de adenocarcinoma ductal pancreático e 3) investigar o efeito da combinação do composto PRIMA-1 com o inibidor de desacetilase de histonas butirato de sódio. Para os estudos de expressão gênica, foram conduzidas análises por PCR quantitativo em tempo real (qRT-PCR) para determinar a expressão dos genes KRAS e DPM1 em amostras de saliva. Em relação aos estudos com linhagens celulares de adenocarcinoma ductal pancreático, foram selecionadas três tipos com diferentes padrões de expressão da proteína p53: PANC-1 (TP53 p.R273H), CAPAN-2 (TP53 wild-type) e BxPC-3 (TP53 p.Y220C) foram utilizadas como modelos in vitro. Para avaliar a resposta celular às drogas, foram realizados estudos de viabilidade celular (MTT), apoptose (AnexinaV/FITC), ciclo celular (BrDU), western-blot e transfecção por siRNAs. Em relação às análises de expressão gênica em saliva, encontramos uma diferença significativa na expressão de KRAS em amostras de câncer de pâncreas, quando comparado aos níveis de expressão em amostras de indivíduos controles. No entanto, uma alta expressão foi detectada também em amostras de pacientes com pancreatite crônica, sugerindo uma baixa especificidade para esse marcador. Nos estudos com novas terapias, observamos que o emprego do composto PRIMA-1 induziu a apoptose de forma seletiva nas células com p53 mutante (PANC-1), redução na síntese de DNA e parada no ciclo celular (G2/M) 12h após o tratamento na dose de 75 μM, efeito que foi intensificado pela associação com o inibidor de desacetilase de histonas butirato de sódio. Os resultados encontrados indicam que o gene KRAS pode ser um potencial biomarcador para o diagnóstico não invasivo de doenças pancreáticas, merecendo estudos complementares e com um número maior de amostra. Também indicam que o composto PRIMA-1 é capaz de controlar a proliferação e induzir apoptose de forma sustentada em células de câncer de pâncreas com mutações no gene TP53, sugerindo um novo alvo potencial para o tratamento dessa…
Advisors/Committee Members: Prolla, Patrícia Ashton.
Subjects/Keywords: Adenocarcinoma ductal pancreático; Biomarcadores; MicroRNAs
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Ribeiro, P. L. I. (2014). Biomarcadores e novas terapias no diagnóstico e tratamento do adenocarcinoma ductal pancreático : estudos de expressão gênica e resposta celular. (Thesis). Universidade do Rio Grande do Sul. Retrieved from http://hdl.handle.net/10183/117905
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Ribeiro, Patrícia Lisbôa Izetti. “Biomarcadores e novas terapias no diagnóstico e tratamento do adenocarcinoma ductal pancreático : estudos de expressão gênica e resposta celular.” 2014. Thesis, Universidade do Rio Grande do Sul. Accessed February 24, 2021.
http://hdl.handle.net/10183/117905.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Ribeiro, Patrícia Lisbôa Izetti. “Biomarcadores e novas terapias no diagnóstico e tratamento do adenocarcinoma ductal pancreático : estudos de expressão gênica e resposta celular.” 2014. Web. 24 Feb 2021.
Vancouver:
Ribeiro PLI. Biomarcadores e novas terapias no diagnóstico e tratamento do adenocarcinoma ductal pancreático : estudos de expressão gênica e resposta celular. [Internet] [Thesis]. Universidade do Rio Grande do Sul; 2014. [cited 2021 Feb 24].
Available from: http://hdl.handle.net/10183/117905.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Ribeiro PLI. Biomarcadores e novas terapias no diagnóstico e tratamento do adenocarcinoma ductal pancreático : estudos de expressão gênica e resposta celular. [Thesis]. Universidade do Rio Grande do Sul; 2014. Available from: http://hdl.handle.net/10183/117905
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Universidade do Rio Grande do Sul
14.
Gromann, Lorrayne Gomes Molina.
Identificação e análise de expressão de microRNAs em tecidos florais de soja (Glycine max (L.) Merrill).
Degree: 2012, Universidade do Rio Grande do Sul
URL: http://hdl.handle.net/10183/54415
► A soja é uma das culturas mais importantes a nível mundial, devido à produção de óleo e a seu alto teor proteico. A fase reprodutiva…
(more)
▼ A soja é uma das culturas mais importantes a nível mundial, devido à produção de óleo e a seu alto teor proteico. A fase reprodutiva é a mais importante para a produtividade da soja, visto que seu cultivo se destina principalmente à produção de grãos. Os microRNAs (miRNAs) desempenham funções essenciais em diversos aspectos do desenvolvimento reprodutivo, incluindo o florescimento, a fertilidade e o desenvolvimento da semente. A função destes pequenos RNAs (sRNAs) endógenos não codificantes é regular a expressão gênica, principalmente através de clivagem e inibição da tradução de mRNAs alvos. A identificação de miRNAs ainda não está saturada e, em soja, não há trabalhos relacionando-os aos diferentes órgãos florais, que são fundamentais na produtividade desta cultura. Neste estudo, amostras de flores, carpelos, estames e pétalas de soja foram usadas na construção de quatro bibliotecas de sRNAs sequenciadas utilizando a plataforma Solexa, gerando um total de 13.557.795 sequências. Através da análise do mapeamento das sequências de sRNAs das bibliotecas em candidatos a precursores de miRNAs de soja identificados, 276 foram considerados precursores autênticos, incluindo 143 precursores novos. Foram identificados 235 miRNAs maduros, dos quais 51 são miRNAs inéditos, pertencentes a 40 novas famílias. Os demais miRNAs identificados pertencem a 64 famílias conhecidas de miRNAs de plantas, das quais três ainda não tinham sido reportadas em soja. Todas as famílias de miRNAs que estão envolvidas na regulação do florescimento foram identificadas entre as mais frequentes nos tecidos florais de soja. Na análise de expressão pela frequência de sequências nas bibliotecas de sRNAs de carpelos, estames e pétalas, 67.2% (158) dos miRNAs identificados foram diferencialmente expressos. Análises de expressão por PCR quantitativa (RT-qPCR) comprovaram a expressão diferencial de 19 miRNAs. O miRNA inédito denominado NF13 apresentou a maior diferença entre os tecidos, sendo fortemente induzido nos carpelos. Para os miRNAs com expressão diferencial comprovada por RT-qPCR foi feita a predição computacional dos genes alvos, para muitos dos quais já foram descritas funções relacionadas ao processo reprodutivo em plantas. O estudo da regulação destes genes pelos miRNAs em diferentes tecidos e estádios de desenvolvimento floral contribuirá para o entendimento dos mecanismos moleculares envolvidos na reprodução da soja.
Soybean is one of the most important crops worldwide, due to the production of oil and its high protein content. The reproductive phase is considered the most important for the yield of soybean, which is mainly intended to produce the grains. MicroRNAs (miRNAs) play essential roles in various aspects of reproductive development, including flowering, fertility and seed development. The function of these endogenous small non-coding RNAs (sRNAs) is to regulate gene expression, mainly through cleavage and translation inhibition of target mRNAs. The identification of miRNAs is not yet saturated in soybeans, and there are no studies…
Advisors/Committee Members: Margis, Rogerio.
Subjects/Keywords: Soja; MicroRNAs; Glycine max
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Gromann, L. G. M. (2012). Identificação e análise de expressão de microRNAs em tecidos florais de soja (Glycine max (L.) Merrill). (Thesis). Universidade do Rio Grande do Sul. Retrieved from http://hdl.handle.net/10183/54415
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Gromann, Lorrayne Gomes Molina. “Identificação e análise de expressão de microRNAs em tecidos florais de soja (Glycine max (L.) Merrill).” 2012. Thesis, Universidade do Rio Grande do Sul. Accessed February 24, 2021.
http://hdl.handle.net/10183/54415.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Gromann, Lorrayne Gomes Molina. “Identificação e análise de expressão de microRNAs em tecidos florais de soja (Glycine max (L.) Merrill).” 2012. Web. 24 Feb 2021.
Vancouver:
Gromann LGM. Identificação e análise de expressão de microRNAs em tecidos florais de soja (Glycine max (L.) Merrill). [Internet] [Thesis]. Universidade do Rio Grande do Sul; 2012. [cited 2021 Feb 24].
Available from: http://hdl.handle.net/10183/54415.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Gromann LGM. Identificação e análise de expressão de microRNAs em tecidos florais de soja (Glycine max (L.) Merrill). [Thesis]. Universidade do Rio Grande do Sul; 2012. Available from: http://hdl.handle.net/10183/54415
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Universidade do Rio Grande do Sul
15.
Santos, Francine Melise dos.
Análise de microRNAs-LIKE em cryptococcus gattii.
Degree: 2013, Universidade do Rio Grande do Sul
URL: http://hdl.handle.net/10183/96872
► O complexo Cryptococcus possui 37 espécies descritas, das quais se destacam C. neoformans e C. gattii devido a sua capacidade de causar doença tanto em…
(more)
▼ O complexo Cryptococcus possui 37 espécies descritas, das quais se destacam C. neoformans e C. gattii devido a sua capacidade de causar doença tanto em humanos como animais. A fim de se prevenir de organismos patogênicos, o hospedeiro pode reduzir a disponibilidade de nutrientes em um processo conhecido como imunidade nutricional. Além disso, é bem descrito o papel central de metais essenciais em relação à expressão dos fatores de virulência nas espécies patogênicas do gênero Cryptococcus. MicroRNAs (miRNAs) são importantes mediadores da expressão gênica em resposta a estresses, incluindo privação de metais ou toxicidade causada pelos mesmos. Entretanto, pouco é conhecido sobre expressão de miRNAs ou miRNAs-like em C. gattii. Portanto, o objetivo desde trabalho foi determinar o perfil miRNAs ou miRNAs-like produzidos por C. gattii durante privação de ferro e privação de zinco. Células de C. gattii R265 foram cultivadas em três condições: privação de zinco, privação de ferro e condição controle. As sequências dos pequenos RNAs foram obtidas por RNA-Seq. A fim de identificar miRNAs em C. gattii, as sequências não redundantes foram alinhadas às sequências dos genomas das linhagens de C. gattii R265 e WM276. Foi realizada a predição de miRNAs ou microRNA-like com ferramentas de bioinformática que resultou em 31 possíveis miRNAs na linhagem R265 e 26 na linhagem WM276, respectivamente. Análises in silico da expressão diferencial dos miRNAs mostraram que a maioria está presente nas três condições, ao passo que apenas dois estão presentes apenas nas condições de privação de metais. Desta forma, estes miRNAs-like podem estar exercendo algum papel importante na homeostase de metais em resposta a condições que mimetizam o ambiente de infecção. Visto que a linhagem R265 de C. gattii não possui um gene codificador da proteína Argonauta, a qual desempenha um papel central na via de RNA de interferência (RNAi), esta via possivelmente não seria responsável pelo silenciamento de outros genes. Levanta-se a hipótese que estes miRNAs-like poderiam ser exportados da célula e, então, modular a expressão gênica no hospedeiro. Esta análise foi iniciada pela avaliação de possíveis alvos expressos pelos genomas de camundongo e humano. Alguns destes alvos mostraram relação com a resposta imune nos hospedeiros. Esta identificação deve esclarecer o papel desenvolvido por miRNAs na regulação da expressão gênica na interação patógeno-hospedeiro.
The Cryptococcus complex has 37 species described, from which C. neoformans and C. gattii stand out for their ability to cause disease in humans and animals. To prevent infection with pathogenic microorganisms, host may reduce the availability of nutrients in a process known as nutritional immunity. Furthermore, it is well described that essential metals have central roles related to the regulation of expression of virulence factors in pathogenic Cryptococcus species. MicroRNAs (miRNAs) are important mediators of gene expression in response to several stresses, including metal deprivation or toxicity.…
Advisors/Committee Members: Staats, Charley Christian.
Subjects/Keywords: Cryptococcus gattii; Criptococose; MicroRNAs
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Santos, F. M. d. (2013). Análise de microRNAs-LIKE em cryptococcus gattii. (Thesis). Universidade do Rio Grande do Sul. Retrieved from http://hdl.handle.net/10183/96872
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Santos, Francine Melise dos. “Análise de microRNAs-LIKE em cryptococcus gattii.” 2013. Thesis, Universidade do Rio Grande do Sul. Accessed February 24, 2021.
http://hdl.handle.net/10183/96872.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Santos, Francine Melise dos. “Análise de microRNAs-LIKE em cryptococcus gattii.” 2013. Web. 24 Feb 2021.
Vancouver:
Santos FMd. Análise de microRNAs-LIKE em cryptococcus gattii. [Internet] [Thesis]. Universidade do Rio Grande do Sul; 2013. [cited 2021 Feb 24].
Available from: http://hdl.handle.net/10183/96872.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Santos FMd. Análise de microRNAs-LIKE em cryptococcus gattii. [Thesis]. Universidade do Rio Grande do Sul; 2013. Available from: http://hdl.handle.net/10183/96872
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
16.
Moreira, Lúcia Margarida Ferreira.
Reprogramação da diferenciação por miRNAs dependentes de CDX2.
Degree: 2017, RCAAP
URL: http://www.rcaap.pt/detail.jsp?id=oai:http://repositorio.utad.pt/:10348/7997
► Dissertação de Mestrado em Biotecnologia para as Ciências da Saúde
No trato gastrointestinal, SOX2 e CDX2 são os fatores de transcrição chave para a diferenciação…
(more)
▼ Dissertação de Mestrado em Biotecnologia para as Ciências da Saúde
No trato gastrointestinal, SOX2 e CDX2 são os fatores de transcrição chave para
a diferenciação dos tecidos, particularmente esófago, estômago e intestino. Na parte
anterior o SOX2 tem um papel ativo na regulação da diferenciação da mucosa esofágica
e gástrica, enquanto na parte posterior é o CDX2 que desempenha um papel essencial
na diferenciação intestinal. Sabe-se que a expressão de SOX2 e CDX2 é mutuamente
exclusiva, em tecidos normais. Para além disso, experiências em modelos animais
mostraram que quando se diminui a expressão de SOX2 ocorre um aumento de CDX2
e vice-versa.
As células com perda total de expressão do gene CDX2 têm um aumento da
expressão do gene SOX2, demonstrando uma interligação na expressão destas
proteínas. Uma vez que não é conhecida atividade repressora de CDX2 tentou-se
estudar uma regulação negativa mediada por microRNAs,
Recorrendo a um array de 754 microRNAs foram selecionados 106 que
obtiveram um Ct<32 tendo sido normalizados para os 3 housekeepings, e para a média
de todos os microRNAs. Para obter uma lista mais restrita e possivelmente mais robusta
de microRNAs diferencialmente expressos nas 3 linhas celulares em estudo,
selecionamos os miRNAs que apareceram diferencialmente expressos quando a
normalização foi feita utilizando a média e pelo menos um dos 3 housekeepings.
Obtivemos uma lista de 10 potenciais microRNAs de interesse regulados por CDX2.
Com recurso à base de dados miRanda e pesquisa bibliográfica fomos investigar quais
desses miRNAs poderiam regular o mRNA SOX2. Selecionamos os let-7d, miR-27b e
miR-19a para validação. O miR-19a e miR-let7d não foram validados, em contrapartida
o miR-27b demonstrou um aumento significativo da sua expressão na linha que
expressa CDX2 o que pode significar a sua regulação por CDX2. Futuramente este
microRNA será estudado quanto ao seu efeito no mRNA de SOX2.
In the gastrointestinal tract, SOX2 and CDX2 are key transcription factors for
tissues differentiation, particularly esophagus, stomach and intestine. SOX2 has an
active role in the regulation of differentiation of esophageal and gastric mucosa, while
CDX2 has an essential role in the intestinal differentiation. It is known that expression of
SOX2 and CDX2 is mutually exclusive in normal tissues. Furthermore, experiments in
animal have shown that when SOX2 expression decreases, CDX2 increased and vice
versa.
Cells with total loss of CDX2 gene expression have an increased expression of
SOX2 gene, showing an interconnection in the expression of these proteins. Since it is
not known any repressor activity of CDX2 it was put to the test a down regulation
mediated by microRNAs.
Using an array of 754 microRNAs were selected 106, which obtained a Ct <32
being normalized for 3 housekeeping’s, and for global averages. To obtain a more
restricted list and possibly more robust of microRNAs differentially expressed in 3 cell
lines under study, we selected miRNAs that appeared differentially expressed when the
normalization…
Advisors/Committee Members: Almeida, Raquel Maria da Silva Graça, Barros, Rita Henriques Pinto de.
Subjects/Keywords: Neoplasias; Cólon; MicroRNAs; Reprogramação
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Moreira, L. M. F. (2017). Reprogramação da diferenciação por miRNAs dependentes de CDX2. (Thesis). RCAAP. Retrieved from http://www.rcaap.pt/detail.jsp?id=oai:http://repositorio.utad.pt/:10348/7997
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Moreira, Lúcia Margarida Ferreira. “Reprogramação da diferenciação por miRNAs dependentes de CDX2.” 2017. Thesis, RCAAP. Accessed February 24, 2021.
http://www.rcaap.pt/detail.jsp?id=oai:http://repositorio.utad.pt/:10348/7997.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Moreira, Lúcia Margarida Ferreira. “Reprogramação da diferenciação por miRNAs dependentes de CDX2.” 2017. Web. 24 Feb 2021.
Vancouver:
Moreira LMF. Reprogramação da diferenciação por miRNAs dependentes de CDX2. [Internet] [Thesis]. RCAAP; 2017. [cited 2021 Feb 24].
Available from: http://www.rcaap.pt/detail.jsp?id=oai:http://repositorio.utad.pt/:10348/7997.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Moreira LMF. Reprogramação da diferenciação por miRNAs dependentes de CDX2. [Thesis]. RCAAP; 2017. Available from: http://www.rcaap.pt/detail.jsp?id=oai:http://repositorio.utad.pt/:10348/7997
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Universidade do Rio Grande do Sul
17.
Dutra, Filipe Santos Pereira.
Clonagem e expressão da eIF4E de Echinococcus granulosus : utilização na purificação de mRNAs.
Degree: 2016, Universidade do Rio Grande do Sul
URL: http://hdl.handle.net/10183/141990
► Com base na interação especifica entre o fator de iniciação eucariótico 4E (eIF4E) e o 5’ CAP monometilguanosina (MMGcap) do mRNA foi desenvolvido um eficiente…
(more)
▼ Com base na interação especifica entre o fator de iniciação eucariótico 4E (eIF4E) e o 5’ CAP monometilguanosina (MMGcap) do mRNA foi desenvolvido um eficiente sistema para purificação de mRNA usando um mutante da proteína humana eIF4E. Apesar de o MMGcap ser o mais comum nos mRNAs eucarióticos, em nematoides e platelmintos devido ao processo de trans-splicing há também a presença do 5’ CAP trimetilguanosina (TMGcap). Tendo em vista a capacidade única da eIF4E de helmintos em interagir com ambos MMGcap e TMGcap, nesse trabalho foram analisadas as sequências peptídicas das eIF4E de platelmintos e a aplicação da proteína recombinante eIF4E de Echinococcus granulosus como uma ferramenta para o enriquecimento de amostras com mRNAs a partir de RNA total do parasito. As sequências preditas das eIF4E de platelmintos foram obtidas para 18 platelmintos parasitos e apenas uma isoforma da proteína foi encontrada em cada organismo. Na análise filogenética, essas proteínas formaram um ramo único e divergente, inclusive dos platelmintos de vida livre. A sequência codificante da proteína eIF4E de E. granulosus foi clonada por recombinação in vivo e a proteína recombinante (EgReIF4E) em fusão com a glutationa S-transferase (GST) foi expressa em Escherichia coli. A proteína em fusão foi recuperada a partir da fração solúvel por cromatografia de afinidade, sendo obtido o rendimento de 12,8 mg de proteína por 1 L de cultura. No ensaio de captura de mRNAs através do 5’ CAP pela GST-EgReIF4E foi usado RNA total de E. granulosus e de E. ortleppi. A capacidade da EgReIF4E em capturar mRNAs foi avaliada por RT-qPCR de forma comparativa ao RNA total e aos resultados obtidos de um kit comercial de Oligo-dT. Foram avaliados tanto os genes relacionados ao processo de trans-splicing como os genes que não passam por este processo. Também foi avaliado a presença dos rRNAs nas amostras. Nossos dados preliminares indicam que a EgReIF4E foi capaz de purificar os mRNAs e reduzir os níveis dos rRNAs. Porém, houve perdas significativas de mRNAs, que precisam ser corrigidas. Apesar de promissora para platelmintos, a aplicação dessa metodologia precisa ser melhor padronizada visando o aumento do rendimento global do sistema.
Based on the specific interaction between the eukaryotic initiation factor 4E (eIF4E) and the mRNA 5 'CAP monometilguanosina (MMGcap), an efficient system for mRNA purification using a mutant of the human protein eIF4E has been developed. Despite of the MMGcap be the most common in eukaryotic mRNAs, in in parasitic nematodes and flatworms due to the trans-splicing process there is also the 5 'CAP trimetilguanosina (TMGcap). Due to this peculiarity and unique ability of the helminthes eIF4E in interacting with both MMGcap and TMGcap, in this work was analyzed the sequences of eIF4E from flatworms and evaluated the using of eIF4E from E. granulosus (Eg-eIF4E) be used as a tool for purification of mRNA derived from total RNA of the parasite. The predicted sequence of the eIF4E flatworms was obtained for 18 parasitic flatworms and…
Advisors/Committee Members: Zaha, Arnaldo.
Subjects/Keywords: Echinococcus granulosus; MicroRNAs; Expressão gênica
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Dutra, F. S. P. (2016). Clonagem e expressão da eIF4E de Echinococcus granulosus : utilização na purificação de mRNAs. (Thesis). Universidade do Rio Grande do Sul. Retrieved from http://hdl.handle.net/10183/141990
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Dutra, Filipe Santos Pereira. “Clonagem e expressão da eIF4E de Echinococcus granulosus : utilização na purificação de mRNAs.” 2016. Thesis, Universidade do Rio Grande do Sul. Accessed February 24, 2021.
http://hdl.handle.net/10183/141990.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Dutra, Filipe Santos Pereira. “Clonagem e expressão da eIF4E de Echinococcus granulosus : utilização na purificação de mRNAs.” 2016. Web. 24 Feb 2021.
Vancouver:
Dutra FSP. Clonagem e expressão da eIF4E de Echinococcus granulosus : utilização na purificação de mRNAs. [Internet] [Thesis]. Universidade do Rio Grande do Sul; 2016. [cited 2021 Feb 24].
Available from: http://hdl.handle.net/10183/141990.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Dutra FSP. Clonagem e expressão da eIF4E de Echinococcus granulosus : utilização na purificação de mRNAs. [Thesis]. Universidade do Rio Grande do Sul; 2016. Available from: http://hdl.handle.net/10183/141990
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Universidade do Rio Grande do Sul
18.
Lima, Júlio César de.
MicroRNAs como reguladores do desenvolvimento em plantas e o papel regulatório em raízes de arroz (Oryza sativa L.) na resposta ao alumínio.
Degree: 2011, Universidade do Rio Grande do Sul
URL: http://hdl.handle.net/10183/29994
► Diversos trabalhos demonstram que a resposta das plantas ao alumínio é complexa. Porém, nenhum trabalho caracterizou o envolvimento de microRNAs nesta resposta. Parte deste trabalho…
(more)
▼ Diversos trabalhos demonstram que a resposta das plantas ao alumínio é complexa. Porém, nenhum trabalho caracterizou o envolvimento de
microRNAs nesta resposta. Parte deste trabalho visou caracterizar o perfil de expressão de diferentes famílias de
microRNAs em resposta ao alumínio comparando-se as raízes de plantas de arroz japonica e indica. De um total de dezesseis
microRNAs diferencialmente expressos, treze
microRNAs tiveram a expressão reduzida e outros seis tiveram a expressão aumentada nas raízes de plantas de arroz japonica tratadas com 450 M de AlCl3 após 8h. Nas plantas de arroz indica tratadas nas mesmas condições, nove
microRNAs foram detectados como diferencialmente expressos. Destes, quatro tiveram a expressão aumentada e os outros cinco tiveram a expressão reduzida. Por RT-qPCR foram confirmados dois alvos do miR528. Um dos alvos, o gene L-Ascorbato Oxidase está relacionado com a regulação da divisão celular. Sugere-se que a regulação pelo miR528 pode estar de acordo com a inibição do desenvolvimento das raízes em resposta ao alumínio em plantas sensíveis. Estes resultados demonstram que a resposta dos
microRNAs ao tratamento com alumínio também é complexa, pois vários
microRNAs, que provavelmente regulam alvos distintos tiveram sua expressão modulada após o tratamento das plantas. Já foi demonstrado que o desenvolvimento de raízes laterais sofre regulação por
microRNAs em Arabidopsis. A outra parte deste trabalho visou caracterizar funcionalmente o miR164 e a expressão espacial de diferentes membros da família miR164 em raízes de plantas de arroz. Plantas superexpressando o miR164 apresentaram as raízes laterais reduzidas em comparação com as plantas não transformadas. Interessantemente, a análise por RT-qPCR de dois alvos do miR164 revelaram resultados inversos. A análise das plantas contendo os promotores de três genes da família miR164 fusionados ao gene repórter GUS revelou uma sobreposição da expressão espacial no órgão. Os
microRNAs miR164a e miR164d localizam-se nas raízes laterais, e o miR164f está localizado nas raízes laterais e também na raiz primária. Porém, cortes transversais das raízes demonstraram que os miR164a e o miR164f localizam-se na endoderme e no estelo, respectivamente. Uma análise in silico das seqüências dos promotores dos seis membros da família miR164 e de seus respectivos alvos revelou a presença de motivos de DNA provavelmente responsivos a fatores de transcrição envolvidos no desenvolvimento de meristemas primários. Com base nestes resultados, sugere-se que os
microRNAs miR164a e miR164f devem estar regulando seus alvos em diferentes tecidos da raiz. Este resultado está de acordo com o desenvolvimento inicial das raízes laterais, pois estas se originam do periciclo componente do estelo. Os
microRNAs têm função crucial ao longo do desenvolvimento e em resposta a estresses abióticos. O papel regulatório dos
microRNAs reside na complexidade e diversidade das respostas a estresses abióticos e ao desenvolvimento, visto que diversos
microRNAs, que provavelmente regulam…
Advisors/Committee Members: Margis, Rogerio.
Subjects/Keywords: MicroRNAs; Arroz; Oryza sativa
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Lima, J. C. d. (2011). MicroRNAs como reguladores do desenvolvimento em plantas e o papel regulatório em raízes de arroz (Oryza sativa L.) na resposta ao alumínio. (Thesis). Universidade do Rio Grande do Sul. Retrieved from http://hdl.handle.net/10183/29994
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Lima, Júlio César de. “MicroRNAs como reguladores do desenvolvimento em plantas e o papel regulatório em raízes de arroz (Oryza sativa L.) na resposta ao alumínio.” 2011. Thesis, Universidade do Rio Grande do Sul. Accessed February 24, 2021.
http://hdl.handle.net/10183/29994.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Lima, Júlio César de. “MicroRNAs como reguladores do desenvolvimento em plantas e o papel regulatório em raízes de arroz (Oryza sativa L.) na resposta ao alumínio.” 2011. Web. 24 Feb 2021.
Vancouver:
Lima JCd. MicroRNAs como reguladores do desenvolvimento em plantas e o papel regulatório em raízes de arroz (Oryza sativa L.) na resposta ao alumínio. [Internet] [Thesis]. Universidade do Rio Grande do Sul; 2011. [cited 2021 Feb 24].
Available from: http://hdl.handle.net/10183/29994.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Lima JCd. MicroRNAs como reguladores do desenvolvimento em plantas e o papel regulatório em raízes de arroz (Oryza sativa L.) na resposta ao alumínio. [Thesis]. Universidade do Rio Grande do Sul; 2011. Available from: http://hdl.handle.net/10183/29994
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
19.
Muller-Coan, Barbara Grasiele [UNESP].
Efeitos da oncoproteína LMP1 do vírus de Epstein-Barr no potencial de invasão e na expressão de microRNAs endógenos em células humanas in vitro.
Degree: 2016, Universidade Estadual Paulista
URL: http://hdl.handle.net/11449/144990
► O vírus Epstein-Barr (Epstein-Barr virus - EBV) é um herpesvírus ubíquo que participa na patogênese de diferentes neoplasias malignas humanas, notadamente o linfoma de Burkitt…
(more)
▼ O vírus Epstein-Barr (Epstein-Barr virus - EBV) é um herpesvírus ubíquo que participa na patogênese de diferentes neoplasias malignas humanas, notadamente o linfoma de Burkitt endêmico e o carcinoma indiferenciado de nasofaringe. Tem tropismo principalmente por células epiteliais e linfócitos B e seu ciclo biológico é dividido em fases de infecção lítica e latente. Isolados distintos do EBV podem apresentar propriedades biológicas peculiares: por exemplo, em relação ao isolado viral B95-8, o M81 tem predileção por células epiteliais e é mais suscetível a induzir reativação lítica espontânea. As células neoplásicas latentemente infectadas pelo EBV expressam número limitado de produtos virais, alguns com papel cancerígeno bem documentado. Nesse sentido merece destaque a proteína latente de membrana 1 (Latent Membrane Protein 1 - LMP1), uma proteína transmembrana com propriedades transformantes in vitro e in vivo. Adicionalmente, a expressão de LMP1 em células epiteliais estimula motilidade e invasão celular, o que reflete em na agressividade biológica de carcinomas associados ao EBV. Para esse efeito, LMP1 pode regular a expressão de determinados microRNAs, que por sua vez podem atuar em diversos processos celulares, como progressão do ciclo celular, proliferação celular, metabolismo celular e apoptose. Alguns microRNAs estão envolvidos em condições adversas à saúde, incluindo a carcinogênese, a progressão tumoral e o surgimento do fenótipo de resistência à drogas em cânceres. A expressão de EBV LMP1 contribui no potencial metastático do carcinoma de nasofaringe; entretanto, é desconhecido se a LMP1 de diferentes isolados virais exibem efeitos distintos no que se refere aos fenômenos da progressão de carcinomas. Por essa razão, o presente estudo verificou se as diferentes variantes de LMP1 (e.g., isolados B95-8 e M81) induziram níveis distintos de migração e invasão celular e de expressão de diversos microRNAs. Para tanto, células expressando a proteína LMP1 dos isolados virais B95-8 e M81, foram submetidas a experimento de migração e invasão celular in vitro e análise da expressão dos miRNAs. Quanto à indução de migração e invasão celular, as variantes não apresentaram diferenças significativas, porém, a expressão de microRNAs demonstrou um indício in silico da variante M81 de induzir a regulação negativa de genes envolvidos em estímulos da adesão focal, angiogênese, anti-apoptóticos, modulação da expressão gênica celular, motilidade e proliferação celular.
Epstein-Barr virus (EBV) is a ubiquitous herpesvirus that participates in many human cancers pathogenesis, such as endemic Burkitt lymphoma and undifferentiated nasopharyngeal carcinoma. EBV cycle is divided into the lytic and latent infection and distinct viral strains may present peculiar biological properties; compared to the viral isolate B95-8, M81 has propensity to epithelial cell infection and can more likely induce spontaneous lytic activation. In latently-infected neoplastic cells, EBV expresses a limited set of viral products, some of them with well…
Advisors/Committee Members: Oliveira, Deilson Elgui de [UNESP], Universidade Estadual Paulista (UNESP).
Subjects/Keywords: Epstein-Barr; microRNAs; Carcinoma; LMP1
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Muller-Coan, B. G. [. (2016). Efeitos da oncoproteína LMP1 do vírus de Epstein-Barr no potencial de invasão e na expressão de microRNAs endógenos em células humanas in vitro. (Thesis). Universidade Estadual Paulista. Retrieved from http://hdl.handle.net/11449/144990
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Muller-Coan, Barbara Grasiele [UNESP]. “Efeitos da oncoproteína LMP1 do vírus de Epstein-Barr no potencial de invasão e na expressão de microRNAs endógenos em células humanas in vitro.” 2016. Thesis, Universidade Estadual Paulista. Accessed February 24, 2021.
http://hdl.handle.net/11449/144990.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Muller-Coan, Barbara Grasiele [UNESP]. “Efeitos da oncoproteína LMP1 do vírus de Epstein-Barr no potencial de invasão e na expressão de microRNAs endógenos em células humanas in vitro.” 2016. Web. 24 Feb 2021.
Vancouver:
Muller-Coan BG[. Efeitos da oncoproteína LMP1 do vírus de Epstein-Barr no potencial de invasão e na expressão de microRNAs endógenos em células humanas in vitro. [Internet] [Thesis]. Universidade Estadual Paulista; 2016. [cited 2021 Feb 24].
Available from: http://hdl.handle.net/11449/144990.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Muller-Coan BG[. Efeitos da oncoproteína LMP1 do vírus de Epstein-Barr no potencial de invasão e na expressão de microRNAs endógenos em células humanas in vitro. [Thesis]. Universidade Estadual Paulista; 2016. Available from: http://hdl.handle.net/11449/144990
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
20.
Pierce, Marsha Louise.
Inner Ear Hair Cell Loss and Stereocilia Defects in miR-183 Family Knockout Models.
Degree: PhD, Biomedical Sciences (graduate program), 2015, Creighton University
URL: http://hdl.handle.net/10504/69027
► Hearing loss is the most prevalent sensory defect, and although hearing aids and cochlear implants can provide sensory input, no current therapeutic options exist for…
(more)
▼ Hearing loss is the most prevalent sensory defect, and although hearing aids and cochlear implants can provide sensory input, no current therapeutic options exist for restoration of normal hearing. The microRNA-183 family (miR-183, miR-96, and miR-182) is highly conserved and coordinately expressed in neurosensory cells including hair cells (HCs) and sensory neurons in the inner ear, and mutations in miR-96 cause deafness in both mice and humans. To specifically investigate the effects of miR-183 family member loss-of-function, miR-183/96 and miR-182 knockout (KO) mice were assessed. Behavioral observations and evaluation of Preyer’s reflex were used to grossly assess hair cell function. Stereocilia defects and hair cell loss in mice ranging from birth (postnatal day zero; P0) to P180 were examined by immunofluorescence microscopy (IFM) detection of MyoVIIa, scanning electron microscopy (SEM), and phase contrast microscopy (PCM) of plastic embedded sections through the organ of Corti. Spiral ganglion innervation was evaluated by IFM detection for acetylated tubulin. Targetscan predicted target genes were compared to neonatal and adult hair cell transcriptomes, genes known to cause hereditary hearing loss, and miR-183 familly confirmed target genes in the literature to identify a relevant subset of genes for further evaluation. Here we show that miR-183/96 KO caused delayed stereocilia development, gross stereocilia disorganization, hair cell loss, innervation defects and deafness. Moreover, miR-183/96 heterozygous (HET) and miR-182 KO mice showed relatively subtle stereocilia defects and age-related loss of acoustic startle response. Arhgdia, Sox2 and Tes were co-expressed with miR-183 family members and mildly upregulated in miR-183/96 KO mice, suggesting such targets might play a role in the observed phenotype. Results demonstrate that miR-183 family loss-of-function (LOF) led to stereocilia defects, hair cell loss, and contributing to hearing deficits. The challenge remains to conclusively identify miR-183 family effects on target genes and pathways that support hair cell maintenance and function to provide insight to approaches for preventing hair cell loss.
Advisors/Committee Members: Soukup, Garrett A. (advisor), Pierce, Marsha Louise (cuauthor).
Subjects/Keywords: Hearing Loss; MicroRNAs; Mice, Knockout
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Pierce, M. L. (2015). Inner Ear Hair Cell Loss and Stereocilia Defects in miR-183 Family Knockout Models. (Doctoral Dissertation). Creighton University. Retrieved from http://hdl.handle.net/10504/69027
Chicago Manual of Style (16th Edition):
Pierce, Marsha Louise. “Inner Ear Hair Cell Loss and Stereocilia Defects in miR-183 Family Knockout Models.” 2015. Doctoral Dissertation, Creighton University. Accessed February 24, 2021.
http://hdl.handle.net/10504/69027.
MLA Handbook (7th Edition):
Pierce, Marsha Louise. “Inner Ear Hair Cell Loss and Stereocilia Defects in miR-183 Family Knockout Models.” 2015. Web. 24 Feb 2021.
Vancouver:
Pierce ML. Inner Ear Hair Cell Loss and Stereocilia Defects in miR-183 Family Knockout Models. [Internet] [Doctoral dissertation]. Creighton University; 2015. [cited 2021 Feb 24].
Available from: http://hdl.handle.net/10504/69027.
Council of Science Editors:
Pierce ML. Inner Ear Hair Cell Loss and Stereocilia Defects in miR-183 Family Knockout Models. [Doctoral Dissertation]. Creighton University; 2015. Available from: http://hdl.handle.net/10504/69027

University of Alberta
21.
Liang, Guanxiang.
Transcriptomic changes of the gut in dairy calves during
pre-weaned period.
Degree: PhD, Department of Agricultural, Food, and Nutritional
Science, 2015, University of Alberta
URL: https://era.library.ualberta.ca/files/c47429914t
► Maintenance of the gut health of calves is vital because enteric infections are associated with high mortality during the pre-weaned period. The small intestine is…
(more)
▼ Maintenance of the gut health of calves is vital
because enteric infections are associated with high mortality
during the pre-weaned period. The small intestine is the primary
site of many enteric infections and plays an important role in
protecting the host from pathogenic infection through both barrier
and mucosal immune functions. However, the molecular mechanisms
regulating small intestine development in the pre-weaned calf have
not been well characterized. Four studies (Chapters 2, 3, 4 and 5)
were performed to investigate the expression profiles of
protein-coding genes and microRNAs (miRNAs) in gut tissues of
pre-weaned calves, identify their changes in response to gut
microbial colonization and enteric infection, and elucidate
potential mechanisms of the small intestinal development in the
pre-weaned calves. The expression of miRNAs in the gastrointestinal
tract had dynamic changes during the pre-weaned period, and their
functions were related to the development of intestinal mucosal
immune system Moreover, significant associations between miRNA
expression and microbial populations in the small intestine
provided evidences that miRNAs were involved in mediating
host-microbial interactions. Further transcriptomic analysis
revealed higher expression levels of genes involved in complement
functional pathway, tight junction protein, and IgA complex in the
jejunum than those in the ileum, suggesting the roles of the
jejunum in the immune and barrier functions in pre-weaned calves.
In addition, during the first week after birth, the temporal
expression pattern of tight junction protein genes, antimicrobial
peptide genes, NOD-like receptor genes, a regulatory T cell marker
gene, and cytokine genes suggested that this is a critical
developmental period for intestinal mucosal immune function. An
ileal loop model was used to target Mycobacterium avium subspecies
paratuberculosis (MAP) infection to the ileal region of the small
intestine. Differentially expressed miRNAs and alternatively
spliced genes in the infected versus uninfected ileal segment
revealed significant changes in endothelial cell proliferation,
macrophage maturation and lysosome function as possible mechanisms
by which MAP escapes host immune responses. Finally, the same
surgical model was used to analyze changes in miRNA expression when
the intestinal microbiota was altered by treatment with a
dose-dependent exposure to allicin, an antimicrobial compound
present in garlic. The observed changes in miRNA expression and
their predicted function in lymphocytes development following of
the changes in gut bacterial population changes after antimicrobial
treatment further supported the conclusion that miRNA expression
was associated with microbial colonization and miRNA played a role
in regulating the intestinal mucosal immune system of pre-weaned
calves. In summary, the transcriptomic analysis revealed that the
protein-coding genes and miRNAs are involved in regulating diverse
aspects of small intestinal development that are age-dependent and
vary among…
Subjects/Keywords: gut; transcriptome; microRNAs; calf
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Liang, G. (2015). Transcriptomic changes of the gut in dairy calves during
pre-weaned period. (Doctoral Dissertation). University of Alberta. Retrieved from https://era.library.ualberta.ca/files/c47429914t
Chicago Manual of Style (16th Edition):
Liang, Guanxiang. “Transcriptomic changes of the gut in dairy calves during
pre-weaned period.” 2015. Doctoral Dissertation, University of Alberta. Accessed February 24, 2021.
https://era.library.ualberta.ca/files/c47429914t.
MLA Handbook (7th Edition):
Liang, Guanxiang. “Transcriptomic changes of the gut in dairy calves during
pre-weaned period.” 2015. Web. 24 Feb 2021.
Vancouver:
Liang G. Transcriptomic changes of the gut in dairy calves during
pre-weaned period. [Internet] [Doctoral dissertation]. University of Alberta; 2015. [cited 2021 Feb 24].
Available from: https://era.library.ualberta.ca/files/c47429914t.
Council of Science Editors:
Liang G. Transcriptomic changes of the gut in dairy calves during
pre-weaned period. [Doctoral Dissertation]. University of Alberta; 2015. Available from: https://era.library.ualberta.ca/files/c47429914t
22.
Alevizos, Ilias.
Μελέτη ρύθμισης γονιδιακής έκφρασης στο σύνδρομο Sjögren.
Degree: 2014, National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ)
URL: http://hdl.handle.net/10442/hedi/42121
► Το σύνδρομο Sjögren χαρακτηρίζεται από στοιχεία συστημικής αυτοανοσίας και δυσλειτουργίας και φλεγμονής στους εξωκρινείς αδένες. Η ακριβής αιτία της εξωκρινούς δυσλειτουργίας στο SS δεν έχει…
(more)
▼ Το σύνδρομο Sjögren χαρακτηρίζεται από στοιχεία συστημικής αυτοανοσίας και δυσλειτουργίας και φλεγμονής στους εξωκρινείς αδένες. Η ακριβής αιτία της εξωκρινούς δυσλειτουργίας στο SS δεν έχει διασαφηνιστεί αλλά θεωρείται ότι συνεισφέρουν σημαντικά μεσολαβούμενοι από το ανοσοποιητικό αλλά και μη ανοσοποιητικοί μηχανισμοί. Η διάγνωση βασίζεται στο συνδυασμό υποκειμενικών συμπτωμάτων και αντικειμενικών σημείων όπως στεγνού στόματος ή/και ξηροφθαλμίας, παρουσίας αυτοαντισωμάτων και φλεγμονώδους διήθησης στους δευτερεύοντες σιελογόνους αδένες.Τα μόρια microRNA (miRNAs) είναι μια ομάδα μικρών μορίων RNA, μήκους 21-24 νουκλεοτιδίων, που εμπλέκονται στη ρύθμιση μιας ευρείας ποικιλίας κυτταρικών και φυσιολογικών διαδικασιών[1-3]. Ασκούν τις επιδράσεις τους με δύο μηχανισμούς: με αποδόμηση του αγγελιοφόρου RNA και διακοπή της μετάφραση. Ένα μοναδικό μόριο mRNA συνήθως μεταφράζεται σε μια μόνο πρωτεΐνη. Ωστόσο, ένα μοναδικό μόριο microRNA είναι ικανό να ρυθμίζει τη μετάφραση πολλαπλών γονιδίων που εμπλέκονται σε μια συγκεκριμένη λειτουργία. Οι αλλαγές στα επίπεδα μεμονωμένων μορίων mRNA μπορεί τελικά να τροποποιηθούν ή να εκμηδενιστούν από τη μετα-μεταφραστική ρύθμιση και έτσι να είναι λιγότερο αντιπροσωπευτικές της φυσιολογικής κατάστασης του κυττάρου σε σχέση με τα μόρια microRNA. Σε αυτή τη διατριβή παρουσιάζουμε τρείς διαφορετικές μελέτες σχετιζόμενες με το ρόλο των μορίων microRNA σto σύνδρομο Sjögren.Η πρώτη μελέτη εξερευνεί τη δυνατότητας χρήσης των μορίων microRNA ως διαγνωστικών και λειτουργικών βιοδεικτών στις αυτοάνοσες νόσους. Συγκεκριμένα, χρησιμοποιήσαμε μικροσυστοιχίες microRNA για να προσδιορίσουμε το προφίλ των δευτερευόντων σιελογόνων αδένων από άτομα ελέγχου και ασθενείς με πρωτοπαθές σύνδρομο Sjögren. Για να εκτιμηθεί η βιολογική εγκυρότητα των διαφορών στα προφίλ των μορίων microRNA μεταξύ των διαφόρων ομάδων εντοπίσαμε τις προβλεπόμενες ατραπούς–στόχους των διαφορικά εκφρασμένων μορίων microRNA χρησιμοποιώντας το πρόγραμμα Ingenuity Pathway Analysis.Η δεύτερη μελέτη εστιάζεται στην ανακάλυψη μέχρι πρότινος αγνώστων μορίων microRNA στους σιελογόνους αδένες των ασθενών με πρωτοπαθές σύνδρομο Sjögren μέσω της μεθόδου Next Generation Sequencing (NGS - Αλληλούχηση Νέας Γενιάς). Η τρίτη μελέτη εστιάζεται στα εξωσώματα από ανθρώπινη σίελο ως πηγή βιοδεικτών microRNA, παρουσιάζοντας μεθόδους για την απομόνωση των εξωσωμάτων απο σίελο μη διεγερμένης και διεγερμένης ολικής, παρωτιδικής και υπογνάθιας σιέλου.
Subjects/Keywords: Σύνδρομο sjögren; MicroRNAs; Sjogren's syndrome
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APA ·
Chicago ·
MLA ·
Vancouver ·
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to Zotero / EndNote / Reference
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APA (6th Edition):
Alevizos, I. (2014). Μελέτη ρύθμισης γονιδιακής έκφρασης στο σύνδρομο Sjögren. (Thesis). National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ). Retrieved from http://hdl.handle.net/10442/hedi/42121
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Alevizos, Ilias. “Μελέτη ρύθμισης γονιδιακής έκφρασης στο σύνδρομο Sjögren.” 2014. Thesis, National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ). Accessed February 24, 2021.
http://hdl.handle.net/10442/hedi/42121.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Alevizos, Ilias. “Μελέτη ρύθμισης γονιδιακής έκφρασης στο σύνδρομο Sjögren.” 2014. Web. 24 Feb 2021.
Vancouver:
Alevizos I. Μελέτη ρύθμισης γονιδιακής έκφρασης στο σύνδρομο Sjögren. [Internet] [Thesis]. National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ); 2014. [cited 2021 Feb 24].
Available from: http://hdl.handle.net/10442/hedi/42121.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Alevizos I. Μελέτη ρύθμισης γονιδιακής έκφρασης στο σύνδρομο Sjögren. [Thesis]. National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ); 2014. Available from: http://hdl.handle.net/10442/hedi/42121
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Loyola University Chicago
23.
Morris, Niya Latrice.
Role of Micrornas in Impaired Gut Permeability Following
Ethanol and Burn Injury.
Degree: PhD, Cell Biology, Neurobiology and
Anatomy, 2018, Loyola University Chicago
URL: https://ecommons.luc.edu/luc_diss/2831
► Every year there are nearly 500,000 reported burn injuries in the United States; half of which occur under the influence of alcohol. Clinical studies…
(more)
▼ Every year there are nearly
500,000 reported burn injuries in the United States; half of which
occur under the influence of alcohol. Clinical studies have shown
that burn patients who are intoxicated at the time of injury have a
worse prognosis; including increased risk of multiple organ
dysfunction syndrome (MODS) and sepsis. The etiology behind these
pathological consequences of ethanol and burn injury remains to be
elucidated. The Gut-lymph hypothesis of MODS theorizes that trauma
(e.g. ethanol and burn injury) results in a redistribution of blood
flow to protect more vital organs which leads to ischemia/hypoxia
(diminished oxygen delivery) in the intestines. Hypoxia has been
demonstrated to negatively affect microRNA (miR) biogenesis. As
microRNAs are central to many cellular functions; disruption of
these molecules due to hypoxic insult could influence tissue
damage, tight junction protein expression and inflammation.
However, the role of hypoxia in mediating intestinal barrier
disruption following ethanol and burn injury remains largely
unknown. The overall objective of this
dissertation is to examine how hypoxia following ethanol and burn
injury modulates expression of microRNA biogenesis components and
microRNAs resulting intestinal barrier disruption. The central
hypothesis is that, hypoxic insult following acute ethanol
intoxication and burn injury disrupts microRNA biogenesis,
resulting in decreased miR-150 expression in isolated small
intestinal epithelial cells and increased intestinal permeability
in vivo. Our results show that ethanol and burn
injury diminishes expression of tight junction proteins, microRNA
biogenesis components: (drosha and argonaute-2) and select
microRNAs. Furthermore, these changes accompany elevated
inflammation, hypoxia (HIF-1α) and bacterial overgrowth. Treatment
of mice at the time of injury with PX-478, a HIF-1α inhibitor,
restored expression of microRNA biogenesis components, and
normalizes the expression of miRs (-7a and -150). These changes
coincided with reduced microbial overgrowth, increased tight
junction protein expression and decreased intestinal permeability.
Together, this work has illuminated the relationship of hypoxia and
microRNAs and their role in regulation of the intestinal barrier
following ethanol and burn
injury.
Subjects/Keywords: Burn; Ethanol; microRNAs; Biology
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Morris, N. L. (2018). Role of Micrornas in Impaired Gut Permeability Following
Ethanol and Burn Injury. (Doctoral Dissertation). Loyola University Chicago. Retrieved from https://ecommons.luc.edu/luc_diss/2831
Chicago Manual of Style (16th Edition):
Morris, Niya Latrice. “Role of Micrornas in Impaired Gut Permeability Following
Ethanol and Burn Injury.” 2018. Doctoral Dissertation, Loyola University Chicago. Accessed February 24, 2021.
https://ecommons.luc.edu/luc_diss/2831.
MLA Handbook (7th Edition):
Morris, Niya Latrice. “Role of Micrornas in Impaired Gut Permeability Following
Ethanol and Burn Injury.” 2018. Web. 24 Feb 2021.
Vancouver:
Morris NL. Role of Micrornas in Impaired Gut Permeability Following
Ethanol and Burn Injury. [Internet] [Doctoral dissertation]. Loyola University Chicago; 2018. [cited 2021 Feb 24].
Available from: https://ecommons.luc.edu/luc_diss/2831.
Council of Science Editors:
Morris NL. Role of Micrornas in Impaired Gut Permeability Following
Ethanol and Burn Injury. [Doctoral Dissertation]. Loyola University Chicago; 2018. Available from: https://ecommons.luc.edu/luc_diss/2831

University of Texas Southwestern Medical Center
24.
Younger, Scott Thomas.
Transcriptional Gene Silencing in Mammalian Cells by MicroRNAs That Target Gene Promoters.
Degree: 2011, University of Texas Southwestern Medical Center
URL: http://hdl.handle.net/2152.5/894
► A rich history exists for RNA-based regulation of gene transcription. It was reported more than a decade ago that RNA is capable of inducing DNA…
(more)
▼ A rich history exists for RNA-based regulation of gene transcription. It was reported more than a decade ago that RNA is capable of inducing DNA methylation and transcriptional gene silencing in plants. It was subsequently shown that small RNAs are involved in the establishment of heterochromatic regions of the yeast genome. More recently it has been demonstrated that small duplex RNAs designed to be complementary to gene promoters are potent regulators of gene transcription in mammalian cells.
Potent and robust transcriptional regulation by designed small RNAs suggests the existence of endogenous mechanisms that facilitate recognition of gene promoters by small RNAs in mammalian cells.
microRNAs (miRNAs) are endogenous small RNAs that regulate gene expression post transcriptionally through base complementarity to target sequences within 3’ UTRs of mRNA transcripts. In this body of work I test the hypothesis that miRNAs can also recognize sequences within gene promoters using two alternative approaches.
In the first approach I computationally evaluate the potential for miRNAs to recognize gene promoters by performing a genome-wide survey of putative miRNA target sites within promoter sequences. In the second approach I use the well characterized human progesterone receptor (PR) gene as a model to experimentally validate that miRNAs possess the ability to regulate transcription in a cell culture system.
Upon completion of this work I found that gene promoters are significantly enriched for miRNA target sites. Furthermore, the frequency of miRNA target sites within promoter sequences is comparable to their frequency within 3’ UTRs. I experimentally screened multiple miRNAs predicted to target the PR gene promoter, identified several that were capable of inhibiting transcription of the PR gene, and characterize the mechanism of transcriptional silencing.
miRNAs have been understood to regulate gene expression at the post transcriptional level through recognition of 3’ UTRs within mRNA transcripts. My study extends miRNA function to recognition of sequences within gene promoters. Sequence specific recognition of gene promoters by miRNAs may complement protein transcription factors. In addition, the ability of small RNAs to rapidly evolve specificity for new sequences would have evolutionary advantages.
Advisors/Committee Members: Corey, David R..
Subjects/Keywords: MicroRNAs; Gene Silencing; Transcription, Genetic
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Younger, S. T. (2011). Transcriptional Gene Silencing in Mammalian Cells by MicroRNAs That Target Gene Promoters. (Thesis). University of Texas Southwestern Medical Center. Retrieved from http://hdl.handle.net/2152.5/894
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Younger, Scott Thomas. “Transcriptional Gene Silencing in Mammalian Cells by MicroRNAs That Target Gene Promoters.” 2011. Thesis, University of Texas Southwestern Medical Center. Accessed February 24, 2021.
http://hdl.handle.net/2152.5/894.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Younger, Scott Thomas. “Transcriptional Gene Silencing in Mammalian Cells by MicroRNAs That Target Gene Promoters.” 2011. Web. 24 Feb 2021.
Vancouver:
Younger ST. Transcriptional Gene Silencing in Mammalian Cells by MicroRNAs That Target Gene Promoters. [Internet] [Thesis]. University of Texas Southwestern Medical Center; 2011. [cited 2021 Feb 24].
Available from: http://hdl.handle.net/2152.5/894.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Younger ST. Transcriptional Gene Silencing in Mammalian Cells by MicroRNAs That Target Gene Promoters. [Thesis]. University of Texas Southwestern Medical Center; 2011. Available from: http://hdl.handle.net/2152.5/894
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Texas Southwestern Medical Center
25.
Patrick, David M.
Regulation of Cellular Growth and Differentiation by MicroRNAs -21 and -451.
Degree: 2013, University of Texas Southwestern Medical Center
URL: http://hdl.handle.net/2152.5/1705
► MicroRNAs are small RNAs approximately 20-24 nucleotides in length that are conserved throughout evolution. MicroRNA genes are transcribed by RNA polymerase II and are processed…
(more)
▼ MicroRNAs are small RNAs approximately 20-24 nucleotides in length that are conserved throughout evolution. MicroRNA genes are transcribed by RNA polymerase II and are processed both in the nucleus and the cytoplasm from longer precursor RNAs. Functionally,
microRNAs interact with Argonaute proteins and guide the formation of a complex with messenger RNAs by Watson-Crick base-pair formation between the microRNA and mRNA. This association stimulates the formation of the microRNA-RNA-induced silencing complex which, upon association with essential adaptor molecules such as GW182, recruits transcriptional repressors and mRNA destabilizers. Essential developmental processes such as embryonic stem cell differentiation and cardiovascular development have been shown to be dependent upon
microRNAs.
MicroRNAs also participate in a variety of disease processes including tumorigenesis and cardiovascular disease.
MicroRNA-451 (miR-451) is regulated during erythrocyte terminal differentiation. The expression of miR-451 is restricted to late erythrocyte precursors and terminally differentiated erythrocytes. We therefore hypothesized that miR-451 plays a role in terminal erythroid differentiation. Deletion of miR-451 in mice results in a terminal erythroid differentiation defect both embryonically and in adulthood. These animals display a reduction in hematocrit and an inability to sustain a high erythropoietic rate. Transient inhibition of miR-451 results in the same defect. Transcript profiling of miR-451-/- erythroblasts revealed upregulation of 14-3-3ξ, a molecule implicated in the regulation of hematopoiesis. Knockdown of 14-3-3ξ with shRNA in miR-451-/- erythroblasts attenuates the differentiation defect. These data show the essential role of miR-451 repression of 14-3-3ξ during terminal erythrocyte differentiation. Finally, the potent effect of miR-451 inhibition on erythrocyte production suggests that this strategy may be efficacious for the treatment of polycythemia vera, a myeloproliferative neoplasm characterzed by excessive erythrocyte production. Inhibition of miR-451 in a mouse model of PV significantly reduces disease burden.
MicroRNA-21 (miR-21) is regulated in a variety of both human and mouse models of disease. MiR-21 has been widely reported as a driver of tumorigenesis and is consistently upregulated in cardiac remodeling. It has been suggested that miR-21 plays a protective role during cardiac hypertrophy, however, an opposing report suggests that miR-21 inhibition is beneficial in a mouse model of cardiac remodeling. We therefore hypothesized that miR-21 played an essential role in cardiac hypertrophy and remodeling. Deletion of miR-21 in mice resulted in no observable phenotype. MiR-21-/- displayed cardiac remodeling, cardiac stress-responsive gene activation, and reduction in cardiac function in response to four cardiac stress models: thoracic aortic constriction, angiotensin II infusion, calcineurin overexpression, and myocardial infarction. Moreover, inhibition of miR-21 with an LNA-modified miR-21…
Advisors/Committee Members: Olson, Eric N., MacDonald, Raymond J., Hill, Joseph A., Johnson, Jane E., Huang, Lily.
Subjects/Keywords: Lung Neoplasms; MicroRNAs; Polycythemia Vera
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Patrick, D. M. (2013). Regulation of Cellular Growth and Differentiation by MicroRNAs -21 and -451. (Thesis). University of Texas Southwestern Medical Center. Retrieved from http://hdl.handle.net/2152.5/1705
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Patrick, David M. “Regulation of Cellular Growth and Differentiation by MicroRNAs -21 and -451.” 2013. Thesis, University of Texas Southwestern Medical Center. Accessed February 24, 2021.
http://hdl.handle.net/2152.5/1705.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Patrick, David M. “Regulation of Cellular Growth and Differentiation by MicroRNAs -21 and -451.” 2013. Web. 24 Feb 2021.
Vancouver:
Patrick DM. Regulation of Cellular Growth and Differentiation by MicroRNAs -21 and -451. [Internet] [Thesis]. University of Texas Southwestern Medical Center; 2013. [cited 2021 Feb 24].
Available from: http://hdl.handle.net/2152.5/1705.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Patrick DM. Regulation of Cellular Growth and Differentiation by MicroRNAs -21 and -451. [Thesis]. University of Texas Southwestern Medical Center; 2013. Available from: http://hdl.handle.net/2152.5/1705
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Texas Southwestern Medical Center
26.
Golden, Ryan Joshua.
Regulatory Mechanisms of the MicroRNA Pathway.
Degree: 2017, University of Texas Southwestern Medical Center
URL: http://hdl.handle.net/2152.5/8301
► MicroRNAs (miRNAs) associate with members of the Argonaute protein family and downregulate partially complementary messenger RNAs (mRNAs) (1). miRNA activity is tightly regulated during development…
(more)
▼ MicroRNAs (miRNAs) associate with members of the Argonaute protein family and downregulate partially complementary messenger RNAs (mRNAs) (1). miRNA activity is tightly regulated during development and in normal physiologic settings, while gain or loss of these control mechanisms can contribute to disease (2-4). To identify new mechanisms that regulate the miRNA pathway, we employed CRISPR-Cas9 genome-wide loss-of-function screening (5, 6) coupled with a fluorescent miRNA pathway reporter. These experiments revealed an unanticipated role for the ANKRD52-PPP6C serine/threonine phosphatase complex as a critical regulator of miRNA activity in human cells. Loss of this complex significantly impaired global miRNA function. Genetic and biochemical studies revealed that phosphorylation of Argonaute2 (AGO2) on a set of highly conserved serine residues, S824-S834, blocks target mRNA engagement. Constitutive activity of the ANKRD52-PPP6C complex is necessary to remove these inhibitory phosphates and thereby allow miRNA-mediated silencing. A genome-wide CRISPR-Cas9 suppressor screen performed in ANKRD52-/- cells identified CSNK1A1 as the inhibitory AGO2 kinase that phosphorylates these sites. Together, these findings reveal a previously uncharacterized AGO2 phosphorylation cycle, uncovering a major mechanism through which the miRNA pathway is regulated and highlighting the power of iterative CRISPR-Cas9 screening for the dissection of biological pathways directly in human cells.
Advisors/Committee Members: Mendelson, Carole R., Mendell, Joshua T., Russell, David W., Liu, Qinghua.
Subjects/Keywords: Argonaute Proteins; Gene Silencing; MicroRNAs
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Golden, R. J. (2017). Regulatory Mechanisms of the MicroRNA Pathway. (Thesis). University of Texas Southwestern Medical Center. Retrieved from http://hdl.handle.net/2152.5/8301
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Golden, Ryan Joshua. “Regulatory Mechanisms of the MicroRNA Pathway.” 2017. Thesis, University of Texas Southwestern Medical Center. Accessed February 24, 2021.
http://hdl.handle.net/2152.5/8301.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Golden, Ryan Joshua. “Regulatory Mechanisms of the MicroRNA Pathway.” 2017. Web. 24 Feb 2021.
Vancouver:
Golden RJ. Regulatory Mechanisms of the MicroRNA Pathway. [Internet] [Thesis]. University of Texas Southwestern Medical Center; 2017. [cited 2021 Feb 24].
Available from: http://hdl.handle.net/2152.5/8301.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Golden RJ. Regulatory Mechanisms of the MicroRNA Pathway. [Thesis]. University of Texas Southwestern Medical Center; 2017. Available from: http://hdl.handle.net/2152.5/8301
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Universidade do Rio Grande do Sul
27.
Calloni, Raquel.
Predição de função de RNAs não codificantes característicos do estado tronco embrionário humano através de ferramentas de bioinformática.
Degree: 2017, Universidade do Rio Grande do Sul
URL: http://hdl.handle.net/10183/173128
► O genoma humano tem um tamano aproximado de 3,2 Gb e aproximadamente 74% das suas sequências são transcritas em RNAs. Destes transcritos, cerca de 33…
(more)
▼ O genoma humano tem um tamano aproximado de 3,2 Gb e aproximadamente 74% das suas sequências são transcritas em RNAs. Destes transcritos, cerca de 33 mil não são traduzidos em proteínas, desempenhando seu papel funcional na célula na forma de RNAs. Dentre os trancritos que não codificam proteínas estão os lncRNAs, os pseudogenes e os circRNAs. Inicialmente considerados como ruídos transcricionais, esses RNAs têm chamado cada vez mais a atenção da comunidade científica e têm sido atribuídos a um série de funções celulares. Apesar do crescente número de trabalhos enfocando estes RNAs, pouco se sabe sobre essas moléculas em células-tronco embrionárias (CTEs) humanas, tanto no que se refere ao conjunto de moléculas expressas quanto sobre a função por elas desempenhada. Nesse sentido, este trabalho teve como objetivo identificar os lncRNAs, pseudogenes e circRNAs expressos em células-tronco embrionárias humanas a partir de dados de RNA-seq depositados no banco de dados GEO e inferir, através de ferramentas de bioinformática, as possíveis funções desempenhadas por estas moléculas no estado tronco. As análises revelaram, ao todo 1182 ncRNAs pertencentes as três classes em estudo (lncRNA, n=317; pseudogene, n=585; e circRNA, n=280) no conjunto de dados principal. Quando este foi comparado a outros conjuntos de dados, 87 lncRNAs, 51 pseudogenes e 10 circRNAs foram detectados como transcritos comuns. Dentre os lncRNAs e os pseudogenes, 15 foram selecionados para inferência de função pela abordagem de guilty by association. Foi possível associar RNA selecionados a processos como splicing, organização de cromatina, mitose, ciclo celular, biogênese de ribossomos, reparo de DNA e resposta ao dano, apoptose, organização do citoesqueleto, desenvolvimento embrionário e regulação da diferenciação celular. Além disso, alguns dos RNAs em estudo mostraram-se fortes candidatos a atuarem como competidores endógenos de mRNAs expressos em CTEs. Análises de correlação, de força de ligação ao miRNA e do tipo de seed do sítio de ligação apontaram os pares de mRNAs e ncRNAs AHCY-RP11-253E3.3, F2RL1-EEF1A1P6, HSPD1-SNHG5, INO80-RP11-20D14.6, PARP1-RP11-20D14.6 e PRIM2-GAS5, juntamente com o RNA circular circ-HIPK3, como os RNAs com maior potencial para competirem pelos miRNAs expressos em CTEs. Estes resultados voltam a atenção da pesquisa básica para uma parte pouco conhecida da biologia das CTEs e direcionam futuros experimentos visando a elucidação da função de ncRNAs nesse contexto celular. Ensaios de modulação da expressão dos ncRNAs e a observação concomitante da respostas dos RNAs e proteínas a eles relacionados são o próximo passo para desvendar os mecanismos moleculares através dos quais estes RNAs desempenham seus papeis em CTEs.
The human genome has an average size of 3.2 Gb and approximately 74% of its sequences are transcribed into RNAs. From this transcripts, around 33 thousand are not translated into proteins, performing their cellular roles as RNAs molecules. Among the non-protein coding transcripts are the lncRNAs, the…
Advisors/Committee Members: Bonatto, Diego.
Subjects/Keywords: Células-tronco embrionárias; RNA; MicroRNAs
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Calloni, R. (2017). Predição de função de RNAs não codificantes característicos do estado tronco embrionário humano através de ferramentas de bioinformática. (Thesis). Universidade do Rio Grande do Sul. Retrieved from http://hdl.handle.net/10183/173128
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Calloni, Raquel. “Predição de função de RNAs não codificantes característicos do estado tronco embrionário humano através de ferramentas de bioinformática.” 2017. Thesis, Universidade do Rio Grande do Sul. Accessed February 24, 2021.
http://hdl.handle.net/10183/173128.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Calloni, Raquel. “Predição de função de RNAs não codificantes característicos do estado tronco embrionário humano através de ferramentas de bioinformática.” 2017. Web. 24 Feb 2021.
Vancouver:
Calloni R. Predição de função de RNAs não codificantes característicos do estado tronco embrionário humano através de ferramentas de bioinformática. [Internet] [Thesis]. Universidade do Rio Grande do Sul; 2017. [cited 2021 Feb 24].
Available from: http://hdl.handle.net/10183/173128.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Calloni R. Predição de função de RNAs não codificantes característicos do estado tronco embrionário humano através de ferramentas de bioinformática. [Thesis]. Universidade do Rio Grande do Sul; 2017. Available from: http://hdl.handle.net/10183/173128
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Texas Southwestern Medical Center
28.
Williams, Koriand'r.
Antagonistic Roles of miR-199a-3p/miR-214 and the miR-200 Family in the Regulation of Uterine Contractility During Pregnancy and Labor.
Degree: 2014, University of Texas Southwestern Medical Center
URL: http://hdl.handle.net/2152.5/1413
► Progesterone (P4) and estradiol-17β (E2) play critical and opposing roles in regulating myometrial quiescence and contractility during pregnancy and labor (Kamel et al., 2010). While…
(more)
▼ Progesterone (P4) and estradiol-17β (E2) play critical and opposing roles in regulating myometrial quiescence and contractility during pregnancy and labor (Kamel et al., 2010). While these contrasting hormonal effects are likely mediated via differential regulation of inflammatory and contractile genes, the underlying mechanisms remain incompletely understood.
Recently, we discovered that miR-200 family members, miR-200b and miR-429, and their target, transcription factor ZEB1, serve as P4/progesterone receptor (PR)-mediated regulators of uterine quiescence during pregnancy (Renthal et al., 2010). In the present study, we identified a novel role for another miR-200 family member, miR-200a, to enhance local metabolism of P4 in myometrium and, thus, decrease PR function during the progression towards labor (Williams et. al., 2012a). This occurs via miR-200a repression of signal transducer and activator of transcription (STAT)5b, a transcriptional repressor of the P4-metabolizing enzyme 20α-hydroxysteroid dehydrogenase (20α-HSD). We observed that miR-200a expression increased and STAT5b expression coordinately decreased in myometrium of mice as they progressed to labor and in laboring myometrium from pregnant women. These changes were associated with a dramatic increase in expression and activity of 20α-HSD in laboring myometrium from mouse and human. In a progesterone-withdrawal mouse model of preterm labor, preterm labor was associated with increased miR-200a, decreased STAT5b and enhanced 20α-HSD expression.
In other studies, we also found that levels of the clustered miRNAs, miR-199a-3p and miR-214, were significantly decreased in laboring myometrium of pregnant mice and humans and in a inflammatory mouse model of preterm labor, while the miR-199a-3p/miR-214 target, cyclooxygenase-2 (COX-2), a critical enzyme in synthesis of pro-inflammatory prostaglandins, was coordinately increased (Williams et al., 2012b). The physiological relevance of the labor-associated increase in miR-199a-3p/214 expression was highlighted by the finding that overexpression of miR-199a-3p and miR-214 in cultured human myometrial cells inhibited COX-2 protein and blocked TNF-α-induced myometrial cell contractility. Notably, estrogen and P4 treatment of ovariectomized mice have opposing effects on uterine miR-199a-3p/214 expression that were mediated by ZEB1. Whereas, P4 stimulated ZEB1 and upregulated miR-199a/214 expression in mouse and human myometrium (Renthal et al., 2010), estrogen had an opposing inhibitory effect. Notably, ZEB1/2 inhibit miR-200 family expression. Together, our findings point to the key pivotal roles of myometrial ZEB1 and its miRNA targets as a hormonally-controlled regulators of inflammatory and contractile gene expression in the pregnant uterus during term and preterm labor.
Advisors/Committee Members: Hammer, Robert, Mendelson, Carole R., Mahendroo, Mala, Olson, Eric N..
Subjects/Keywords: Estrogens; Labor, Obstetric; MicroRNAs; Progesterone
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Williams, K. (2014). Antagonistic Roles of miR-199a-3p/miR-214 and the miR-200 Family in the Regulation of Uterine Contractility During Pregnancy and Labor. (Thesis). University of Texas Southwestern Medical Center. Retrieved from http://hdl.handle.net/2152.5/1413
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Williams, Koriand'r. “Antagonistic Roles of miR-199a-3p/miR-214 and the miR-200 Family in the Regulation of Uterine Contractility During Pregnancy and Labor.” 2014. Thesis, University of Texas Southwestern Medical Center. Accessed February 24, 2021.
http://hdl.handle.net/2152.5/1413.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Williams, Koriand'r. “Antagonistic Roles of miR-199a-3p/miR-214 and the miR-200 Family in the Regulation of Uterine Contractility During Pregnancy and Labor.” 2014. Web. 24 Feb 2021.
Vancouver:
Williams K. Antagonistic Roles of miR-199a-3p/miR-214 and the miR-200 Family in the Regulation of Uterine Contractility During Pregnancy and Labor. [Internet] [Thesis]. University of Texas Southwestern Medical Center; 2014. [cited 2021 Feb 24].
Available from: http://hdl.handle.net/2152.5/1413.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Williams K. Antagonistic Roles of miR-199a-3p/miR-214 and the miR-200 Family in the Regulation of Uterine Contractility During Pregnancy and Labor. [Thesis]. University of Texas Southwestern Medical Center; 2014. Available from: http://hdl.handle.net/2152.5/1413
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Texas Southwestern Medical Center
29.
Belkaya, Serkan.
Characterization of Stress Responsive MicroRNAs and Their Roles in T Cell Development.
Degree: 2014, University of Texas Southwestern Medical Center
URL: http://hdl.handle.net/2152.5/1422
► Physiological stress evokes rapid changes in both the innate and adaptive immune responses. Immature αβ T cells developing in the thymus are particularly sensitive to…
(more)
▼ Physiological stress evokes rapid changes in both the innate and adaptive immune responses. Immature αβ T cells developing in the thymus are particularly sensitive to stress, with infections and/or exposure to lipopolysaccharide or glucocorticoids eliciting a rapid apoptotic program.
MicroRNAs (miRs) are short, non-coding RNAs that play critical roles in the immune system by targeting diverse mRNAs. We hypothesized that a subset of thymically encoded miRs would be stress responsive and modulate thymopoiesis. Thymic miR profiling revealed 18 distinct miRs that are dysregulated more than 1.5-fold in response to lipopolysaccharide or the synthetic glucocorticoid dexamethasone. These stress-responsive miRs are dynamically regulated in distinct thymocyte subsets. We utilized both transgenic and gene-targeting approaches to study the impact of these miRs on thymopoiesis under normal and stress conditions.
MiR-181d is the most down-regulated thymic miR in response to stress. The over-expression of miR-181d in developing thymocytes reduced the number of immature CD4+CD8+ thymocytes. Lipopolysaccharide or dexamethasone injections caused a 4-fold greater loss of these cells than in the wild type controls. The targeted elimination of miR-181d resulted in a thymus stress-responsiveness similar to wild-type mice, suggesting a functional redundancy between miR-181 family members. Gene expression comparisons further indicated that miR-181d affects a number of stress, metabolic, and signaling pathways. These findings demonstrate that selected miRs enhance stress-mediated thymic involution in vivo.
MiR-185, another stress-responsive miR in murine thymus, is haploinsufficient in almost all individuals with 22q11.2 deletion/DiGeorge syndrome that can present with immune, cardiac, parathyroid, and psychological problems. The molecular targets of miR-185 in thymocytes are unknown. Transgenic expression of miR-185 attenuated thymopoiesis at the TCRβ-selection checkpoint and during positive selection. This caused a peripheral T cell lymphopenia. Mzb1, NFATc3, and Camk4 were identified as novel miR-185 targets. Elevations in miR-185 enhanced TCR-dependent intracellular calcium levels, while a knockdown of miR-185 diminished these calcium responses. These effects concur with reductions in Mzb1, an endoplasmic reticulum calcium regulator. Consistent with the haploinsufficiency of miR-185, Mzb1 levels were elevated in thymocyte extracts from several 22q11.2 deletion/DiGeorge syndrome patients. These findings indicate that miR-185 regulates T cell development through its targeting of several mRNAs including Mzb1.
Advisors/Committee Members: Hooper, Lora V., van Oers, Nicolai S. C., Chen, Zhijian J., Yarovinsky, Felix, Liou, Jen.
Subjects/Keywords: MicroRNAs; Stress, Physiological; T-Lymphocytes
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Record Details
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Belkaya, S. (2014). Characterization of Stress Responsive MicroRNAs and Their Roles in T Cell Development. (Thesis). University of Texas Southwestern Medical Center. Retrieved from http://hdl.handle.net/2152.5/1422
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Belkaya, Serkan. “Characterization of Stress Responsive MicroRNAs and Their Roles in T Cell Development.” 2014. Thesis, University of Texas Southwestern Medical Center. Accessed February 24, 2021.
http://hdl.handle.net/2152.5/1422.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Belkaya, Serkan. “Characterization of Stress Responsive MicroRNAs and Their Roles in T Cell Development.” 2014. Web. 24 Feb 2021.
Vancouver:
Belkaya S. Characterization of Stress Responsive MicroRNAs and Their Roles in T Cell Development. [Internet] [Thesis]. University of Texas Southwestern Medical Center; 2014. [cited 2021 Feb 24].
Available from: http://hdl.handle.net/2152.5/1422.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Belkaya S. Characterization of Stress Responsive MicroRNAs and Their Roles in T Cell Development. [Thesis]. University of Texas Southwestern Medical Center; 2014. Available from: http://hdl.handle.net/2152.5/1422
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Texas Southwestern Medical Center
30.
Shields, Benjamin Baker.
Mapping the Landscape of Acquired Vulnerabilities in Ovarian Cancer.
Degree: 2013, University of Texas Southwestern Medical Center
URL: http://hdl.handle.net/2152.5/1589
► Recent undertakings to identify the genetic lesions associated with ovarian cancer have noted the striking diversity of mutations occurring in this disease. This genetic diversity…
(more)
▼ Recent undertakings to identify the genetic lesions associated with ovarian cancer have noted the striking diversity of mutations occurring in this disease. This genetic diversity has complicated the search for novel therapies. However, recent data has suggested that one commonality of ovarian tumors might be ablation of miRNA biogenesis. Here I conducted a broad-scale gain-of-function microRNA (miRNA) screen in 16 ovarian cancer cell lines to annotate the functional landscape present in such a chaotic genetic background. miRNAs function as multigenic perturbations allowing for interrogation of maximal gene space with few experiments. This screen identified multiple miRNAs reducing cell viability with the majority of hits being toxic in only one or two lines screened. This surprising finding reflected the commonality of altered miRNA function in ovarian tumors while also suggesting that specifics of this alteration in function are unique to each tumor. To investigate more public vulnerabilities, I focused mechanistic studies on miRNAs displaying penetrance in greater than 5 cell lines. miR-517a reduced cell viability in over 30% of the panel and also reduced tumor burden in vivo. Functional analysis of the predicted targets of miR-517a revealed that expression of this miRNA reduced protein levels of ARCN1, a member of the coatamer complex, and that knockdown of ARCN1 reduced cell viability similar to miR-517a. Another penetrant miRNA, miR-124a, reduced cell viability in 37.5% of the panel and functional analysis of this miRNA revealed it promoted a cell differentiation program. Analysis of predicted targets revealed that expression of miR-124a reduced expression the homeodomain transcription factor SIX4, resulting in increased signaling along the tumor suppressive AMPK pathway and epithelial differentiation. Furthermore, SIX4 displayed increased expression in ovarian tumors and depletion of SIX4 expression reduced tumor cell viability in vitro and in vivo. Therefore, SIX4 overexpression might function to deflect cell differentiation in tumors. Thus, the common loss of miRNA function observed in ovarian tumors might serve to maintain an undifferentiated state, and engagement of cell fate determination programs via re-expression of miRNAs can result in catastrophic consequences for cancer cell viability.
Advisors/Committee Members: Castrillon, Diego H., White, Michael A., Altschuler, Steven J., Brekken, Rolf A..
Subjects/Keywords: Cell Differentiation; MicroRNAs; Ovarian Neoplasms
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Record Details
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Shields, B. B. (2013). Mapping the Landscape of Acquired Vulnerabilities in Ovarian Cancer. (Thesis). University of Texas Southwestern Medical Center. Retrieved from http://hdl.handle.net/2152.5/1589
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Shields, Benjamin Baker. “Mapping the Landscape of Acquired Vulnerabilities in Ovarian Cancer.” 2013. Thesis, University of Texas Southwestern Medical Center. Accessed February 24, 2021.
http://hdl.handle.net/2152.5/1589.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Shields, Benjamin Baker. “Mapping the Landscape of Acquired Vulnerabilities in Ovarian Cancer.” 2013. Web. 24 Feb 2021.
Vancouver:
Shields BB. Mapping the Landscape of Acquired Vulnerabilities in Ovarian Cancer. [Internet] [Thesis]. University of Texas Southwestern Medical Center; 2013. [cited 2021 Feb 24].
Available from: http://hdl.handle.net/2152.5/1589.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Shields BB. Mapping the Landscape of Acquired Vulnerabilities in Ovarian Cancer. [Thesis]. University of Texas Southwestern Medical Center; 2013. Available from: http://hdl.handle.net/2152.5/1589
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
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