Downregulation of DNMT3a expression increases miR-182-induced apoptosis of ovarian cancer through caspase-3 and caspase-9-mediated apoptosis and DNA damage response

作者：Lu, Wei^*; Lu, Tanmin; Wei, Xin

来源：Oncology Reports, 2016, 36(6): 3597-3604.

DOI：10.3892/or.2016.5134

• DNMT3a
• ovarian cancer
• miR482
• caspase-3
• caspase-9
• DNA damage response

In the present study, DNA (cytosine-5)-methyltrans-ferase 3 alpha (DNMT3a) is explored as an anticancer molecule in ovarian cancer treatment, and also the mechanistic link between DNMT3a and its regulatory signaling pathway in Caov-3 cells is provided. Firstly, DNMT3a protein expression in 12 freshly resected ovarian cancer patient tissues and tisssues from 8 ovariectomized patients was assessed. In the ovarian cancer tissues, DNMT3a expression was upregulated and miR-182 expression was downregulated. DNMT3a overexpression inhibited miR-182 expression and caspase-3 and -9 activity and suppressed p53 and c-Myc protein expression in Caov-3 cells. Secondly, miR-182 overexpression increased Caov-3 cell apoptosis, which however was reduced by DNMT3a (DNMT3 plasmid) overexpression. Downregulation of DNMT3a expression activated miR-182 expression and caspase-3 and-9 activity, and promoted p53 and c-Myc protein expression in Caov-3 cells. Collectively, a valuable anticancer mechanism of ovarian cancer was elucidated, by which downregulation of DNMT3a regulated miR-182 via caspase-3 and-9-mediated apoptosis and DNA damage response, which suggests that DNMT3a may be used as a potential strategy for therapeutic intervention in ovarian cancer.

• 出版日期2016-12
• 单位聊城市人民医院