TY - JOUR
T1 - Abstract 1476: Hypermethylation of a TGF-β regulated micro-RNA, miR-193a, predicts prognosis in ovarian cancer
AU - Cheng, Frank Hsueh-Che
AU - Chen, Gary C.W.
AU - Chou, Jian-Liang
AU - Lin, Ya-Wen
AU - Chen, Lin-Yu
AU - Lai, Hung-Cheng
AU - Li, Chin
AU - Chan, Michael W.Y.
PY - 2014/10/1
Y1 - 2014/10/1
N2 - 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
AB - 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
U2 - 10.1158/1538-7445.AM2014-1476
DO - 10.1158/1538-7445.AM2014-1476
M3 - 文章
SN - 0008-5472
VL - 74
SP - 1476
EP - 1476
JO - Cancer Research
JF - Cancer Research
IS - 19_Supplement
ER -
