Abstract 1476: Hypermethylation of a TGF-β regulated micro-RNA, miR-193a, predicts prognosis in ovarian cancer

Abstract

Abstract Ovarian cancer is one of the most lethal cancers in the female reproductive system. One of the hypotheses suggests that ovarian cancer arises from cancer stem/progenitor cell with surface antigen CD117 (or c-kit). In order to identify microRNAs (miRNAs) that can regulate the expression of c-kit, bioinformatic prediction was performed and identified miR-193a as one of the regulators. Expression analysis showed that miR-193a was up-regulated upon TGF-β treatment in immortalized ovarian surface epithelial cells (IOSE) cells. On the contrary, expression of miR-193a cannot be detected in a panel of ovarian cancer cell lines (SKOV3, A2780, CP70, MCP2, MCP3). Bisulphite pyrosequencing revealed that promoter CpG island of miR-193a was not methylated in IOSE cell but hypermethylated in the ovarian cancer cells showing down-regulation of miR-193a. Treatment of 5azaDC, a DNMT inhibitor, partially restored miR-193a expression in the ovarian cancer cells, thus suggesting DNA hypermethylation may be responsible for the down-regulation of miR-193a in ovarian cancer. Further clinical studies using bisulphite pyrosequencing found that promoter region of miR-193a was heavily methylated in 109 ovarian cancer patient samples but not in normal OSE samples. Kaplan-meier analysis revealed that patients with higher methylation of miR-193a was significantly associated with shorter overall survival and progression-free survival. Taken together, miR-193a may be a TGF-β regulated tumor suppressor micro-RNA and is epigenetically silenced in ovarian cancer. Methylation of miR-193a may be able to predict prognosis in ovarian cancer patients. Citation Format: Frank Hsueh-Che Cheng, Gary C.W. Chen, Jian-Liang Chou, Ya-Wen Lin, Lin-Yu Chen, Hung-Cheng Lai, Chin Li, Michael W.Y. Chan. Hypermethylation of a TGF-β regulated micro-RNA, miR-193a, predicts prognosis in ovarian cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1476. doi:10.1158/1538-7445.AM2014-1476