Inhibition of Ovarian Cancer by microRNA-mediated Regulation of Telomerase

摘要

A hallmark of ovarian cancer is its limitless proliferative potential which is governed in part by elevated levels of human telomerase (hTERT) or telomerase activity. However, how telomerase can be regulated in normal cells, and how this regulation can be lost during cancer progression, is not completely understood. microRNAs (miRNAs) are evolutionarily conserved, small, non-coding, single-stranded, approximately 19-23 nucleotide RNA molecules that are estimated to negatively regulate protein encoding genes including those related to cancer development. The objective of this proposal is to determine whether telomerase (hTERT) is negatively regulated by microRNAs in normal ovarian surface epithelial cells and whether the expression of these microRNAs is lost during ovarian cancer progression. Using bioinformatics and databases of microRNAs, we identified putative microRNAs for hTERT. We correlated these microRNAs with their expression in normal ('up') and cancerous ('down') ovarian tissue. This correlation led to a microRNA short-list of potential hits to test for their effect on telomerase activity in ovarian cancer cells. Current studies include validating this list and the long-term effects on cancer cell growth. Telomerase inhibition by microRNAs can thus lead to new therapy as well as understanding how ovarian cancer progresses (from normal, early, then to late stage).