Abstract 1544: Identification of microRNA which regulates peritoneal dissemination of ovarian cancer

Abstract

Abstract Ovarian cancer is highly metastatic and characterized by widespred peritoneal dissemination and massive ascites, and is the leading cause of death from gynecological malignancies. We have previously identified integrin α5 as a promising target for ovarian cancer treatment by inhibiting peritoneal dissemination. Our aim is to newly identify microRNAs which regulate integrin α5 expression and analyze the therapeutic potential of targeting those microRNAs. Based on the microRNA algorism search, we identified hsa-mira-92a as one of the candidates. Hsa-mir-92a is little expressed in ovarian cancer cells which express high level of integrin α5, whereas hsa-mir-92a is highly expressed in RMUG-S cells which hardly express integrin α5. Forced expression of mir-92a in ovarian cancer cell lines reduced integrin α5 expression in mRNA and protein level, accompanied by the inhibition of cell adhesion and invasion. On the contrary, the antagonist of mir-92a enhanced integrin α5 expression in RMUG-S cells. Luciferase assay revealed that mir-92a reduces the transcriptional activity of integrin α5 by directly binding ITGA5 3′-UTR. In vivo ovarian cancer xenografts, transducing hsa-mir-92a expressing plasmid into ovarian cancer cell lines significantly reduced peritoneal dissemination and ascites formation. Those results suggested targeting hsa-mir-92a could be a promising therapy for a subset of ovarian cancer patients by inhibiting integirn α5 expression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1544. doi:10.1158/1538-7445.AM2011-1544