MICRORNA: PROFILING AND FUNCTIONAL IMPLICATIONS IN CANCER AND METABOLISM

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2012-12

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Abstract

MicroRNAs (miRNAs) are a class of ~22 nt short, non-coding RNAs that post-transcriptionally regulate target mRNA expression. To date, ~2,000 mature miRNAs have been identified in humans and they are estimated to regulate about 50% of human genes. miRNAs, due to their ubiquitous target distribution, contribute to diverse processes including cell development, proliferation, differentiation, apoptosis, and metabolism. Dysregulation of miRNA expression has been reported in various cancers and metabolic disorders. miRNA are also implicated in the initiation and progression of those diseases. In my dissertation, I studied the differentially expressed (DE) miRNAs upon prostaglandin E2 (PGE2) stimulation in prostate cancer cells (PC-3). Concurrently I examined mRNA expression profile of the PC-3 system and determined anticorrelated miRNA:mRNA pairs. The DE miRNAs and their putative targets were affected by the induction of PGE2. They were suggested to be involved in PGE2 dysregulated signaling pathways in PC-3 prostate cancer. In the second part of the thesis work, I identified a set of adipose-enriched miRNAs from porcine tissues samples and verified that these miRNAs were conserved in humans. Adipose-enriched miRNAs were reported to be involved in metabolism, inflammation responses, and tumorigenesis. The analysis results of my thesis experiments suggested adipose-enriched miRNAs may have a potential role in connecting obesity, inflammation, and cancer. It is hoped that the understanding of the molecular basis in cancer and metabolic disorders on the miRNA level will provide new diagnostic targets and therapeutic targets for the diseases.

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Keywords

MicroRNAs (miRNA), Prostaglandin E2 (PGE2), Integrative analysis, Porcine adipose-enriched microRNA, Metabolism, Inflammation, Cancer, MiRFocus pathway enrichment analysis

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