期刊
ONCOLOGY REPORTS
卷 36, 期 6, 页码 3597-3604出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/or.2016.5134
关键词
DNMT3a; ovarian cancer; miR482; caspase-3; caspase-9; DNA damage response
类别
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.
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