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You searched for subject:(miR 181b). Showing records 1 – 2 of 2 total matches.

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University of Newcastle

1. Carroll, Adam. Genomic characterisation of small RNA-mediated post-transcriptional gene regulation.

Degree: PhD, 2013, University of Newcastle

Research Doctorate - Doctor of Philosophy (PhD)

microRNA (miRNA) are small non-coding RNA molecules that function to guide the miRNA-induced silencing complex (miRISC) to regions of complementarity within mRNA transcripts, thereby mediating sequence-specific post-transcriptional gene silencing (PTGS). This form of gene regulation is vital to a variety of biological processes in animals, from fundamental developmental functions including cellular proliferation and differentiation, to more complex and specialised roles such as long-term potentiation and synapse-specific modifications in neurons. While the complementarity of miRNA-mRNA interactions enables bioinformatic algorithms to predict potential target genes, the capacity for miRNA to interact with their targets through elements of only partial complementarity renders high false discovery rates to these predictions. With the discovery of increased cortical miRNA expression in schizophrenia, biological evidence was therefore required to investigate the function of schizophrenia-associated miRNA including miR-181b, miR-107, and members of the miR-15 and miR-17 families. Functional genomic techniques were established with genome-wide expression analysis and miRNA reporter-gene assays to characterise the biology of these miRNA in a variety of cellular contexts. In vitro characterisation of miR-181b revealed target gene regulation through interactions at both conserved and non-conserved MREs, with primary and secondary effects of miRNA modulation affecting many genes enriched within neurodevelopmental pathways vital to synaptic plasticity, including a number of schizophrenia candidate genes. Surprisingly, comparisons of miR-181b and miR-107 function against target prediction frameworks revealed a subset of predicted targets displaying positive correlation with cognate miRNA expression. Context-specific functional pleiotropy was also observed in different cellular environments, and this was further explored through miR-17/20a in T lymphocyte activation, and through miR-16 in cell cycle progression. Ultimately, substantial evidence was obtained to establish biological plausibility for miR-181b dysregulation as a potential aetiological factor in the development of schizophrenia, though the emergent theme of context-specific miRNA function requires future methodological developments and experiments to consider this functional pleiotropy when exploring miRNA function in normal developmental and pathophysiological states.

Advisors/Committee Members: University of Newcastle. Faculty of Health & Medicine, School of Biomedical Sciences and Pharmacy.

Subjects/Keywords: miRNA; schizophrenia; thesis by publication; target identification; luciferase assay; miR-181b; miR-107; miR-17; miR-20a; miR-16; expression

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Carroll, A. (2013). Genomic characterisation of small RNA-mediated post-transcriptional gene regulation. (Doctoral Dissertation). University of Newcastle. Retrieved from http://hdl.handle.net/1959.13/1037796

Chicago Manual of Style (16th Edition):

Carroll, Adam. “Genomic characterisation of small RNA-mediated post-transcriptional gene regulation.” 2013. Doctoral Dissertation, University of Newcastle. Accessed December 13, 2019. http://hdl.handle.net/1959.13/1037796.

MLA Handbook (7th Edition):

Carroll, Adam. “Genomic characterisation of small RNA-mediated post-transcriptional gene regulation.” 2013. Web. 13 Dec 2019.

Vancouver:

Carroll A. Genomic characterisation of small RNA-mediated post-transcriptional gene regulation. [Internet] [Doctoral dissertation]. University of Newcastle; 2013. [cited 2019 Dec 13]. Available from: http://hdl.handle.net/1959.13/1037796.

Council of Science Editors:

Carroll A. Genomic characterisation of small RNA-mediated post-transcriptional gene regulation. [Doctoral Dissertation]. University of Newcastle; 2013. Available from: http://hdl.handle.net/1959.13/1037796

2. Wang, Bo. Role of microRNAs in Hepatocarcinogenesis.

Degree: PhD, Molecular, Cellular and Developmental Biology, 2012, The Ohio State University

MicroRNAs are conserved, small (20-25 nucleotide) noncoding RNAs that negatively regulate expression of mRNAs at the post-transcriptional level. MicroRNA signature is altered in different disease states including cancer and some microRNAs act as oncogenes or tumor suppressors. To identify microRNAs that may play a causal role in hepatocarcinogenesis we used an animal model in which C57BL/6 mice fed choline deficient and amino acid defined (CDAA) diet develop nonalcoholic steatohepatitis (NASH)-induced hepatocarcinogenesis after 70 weeks. Microarray analysis identified 30 hepatic microRNAs that are significantly (P<.01) altered in mice fed CDAA diet for 6, 18, 32 and 65 weeks compared to those fed choline sufficient and amino acid defined diet (CSAA). Real-time RT-PCR analysis demonstrated upregulation of oncogenic miR-155, miR-181b, miR-221/222 and miR-21 and downregulation of the most abundant liver specific miR-122 at early stages of hepatocarcinogenesis. Western blot analysis showed reduced expression of hepatic PTEN, a target of miR-21, and C/EBPß, a target of miR-155, in these mice at early stages. DNA binding activity of NF-¿B that transactivates miR-155 gene was significantly (P=0.002) elevated in the liver nuclear extract of mice fed CDAA diet. Further, the expression of miR-155, as measured by in situ hybridization and real-time RT- PCR, correlated with diet-induced histopathological changes in the liver. Ectopic expression of miR-155 promoted growth of hepatocellular carcinoma (HCC) cells whereas its depletion inhibited cell growth. Notably, miR-155 was significantly (P=0.0004) upregulated in primary human HCCs with concomitant decrease (P=0.02) in C/EBPß level compared to matching liver tissues. The expression of tissue inhibitor of metalloprotease 3 (TIMP3), a tumor suppressor and a validated miR-181 target, was markedly suppressed in the livers of mice fed CDAA diet. Upregulation of hepatic transforming growth factor ß (TGFß) and its downstream mediators Smad 2, 3 and 4 and increase in phospho-Smad2 in the liver nuclear extract correlated with elevated miR-181b/d in mice fed CDAA diet. The levels of the precursor and mature miR-181b were augmented on exposure of hepatic cells to TGFß and were significantly reduced by small interference RNA-mediated depletion of Smad4, showing the involvement of TGFß signaling pathway in miR-181b expression. Ectopic expression of miR-181b showed that miR-181b enhanced matrix metallopeptidases 2 (MMP2) and MMP9 activity and promoted growth, clonogenic survival, migration and invasion of HCC cells that could be reversed by modulating TIMP3 level. Further, depletion of miR-181b inhibited tumor growth of HCC cells in nude mice. miR-181b also enhanced resistance of HCC cells to the anticancer drug doxorubicin. Conclusion: Temporal changes in microRNA profile occur at early stages of CDAA diet-induced hepatocarcinogenesis. Reciprocal regulation of specific oncomirs and their tumor suppressor targets implicate their role in NASH-induced… Advisors/Committee Members: Jacob, Samson (Advisor), Ghoshal, Kalpana (Advisor).

Subjects/Keywords: Biomedical Research; Molecular Biology; Hepatocellular carcinoma (HCC); hepatocarcinogenesis; Choline deficient and amino acid defined (CDAA) diet; nonalcoholic steatohepatitis (NASH); microRNA; miR-155; miR-181b

…W, Jacob ST, Ghoshal K. TGFbeta-mediated upregulation of hepatic miR-181b promotes… …46 Chapter 3 TGFβ Mediated Upregulation of Hepatic miR-181b Promotes Hepatocarcinogenesis… …a candidate target of miR-181b, is downregulated at early stages of CDAA dietinduced… …mediators activates miR-181b expression ...80 3.4.4 miR-181b accelerates tumorigenic… …potential of HCC cells….81 3.4.5 TIMP3 modulates biological function of miR-181b ..83 3.4.6 miR… 

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Wang, B. (2012). Role of microRNAs in Hepatocarcinogenesis. (Doctoral Dissertation). The Ohio State University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=osu1329154583

Chicago Manual of Style (16th Edition):

Wang, Bo. “Role of microRNAs in Hepatocarcinogenesis.” 2012. Doctoral Dissertation, The Ohio State University. Accessed December 13, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=osu1329154583.

MLA Handbook (7th Edition):

Wang, Bo. “Role of microRNAs in Hepatocarcinogenesis.” 2012. Web. 13 Dec 2019.

Vancouver:

Wang B. Role of microRNAs in Hepatocarcinogenesis. [Internet] [Doctoral dissertation]. The Ohio State University; 2012. [cited 2019 Dec 13]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1329154583.

Council of Science Editors:

Wang B. Role of microRNAs in Hepatocarcinogenesis. [Doctoral Dissertation]. The Ohio State University; 2012. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1329154583

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