title: Downregulation of DNMT3a expression increases miR-182-induced apoptosis of ovarian cancer through caspase-3 and caspase-9-mediated apoptosis and DNA damage response.
abstract: In the present study, DNA (cytosine-5)-methyltransferase 3α (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.
authors.affiliation: Department of Obstetrics and Gynecology, Liaocheng People's Hospital, Liaocheng, Shandong 252000, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.affiliation: Department of Obstetrics and Gynecology, Liaocheng People's Hospital, Liaocheng, Shandong 252000, P.R. China.
authors.forename: Tanmin
authors.initials: T
authors.lastname: Lu
authors.affiliation: Department of Obstetrics and Gynecology, Liaocheng People's Hospital, Liaocheng, Shandong 252000, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wei
mesh_terms: D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism*; D053453:Caspase 9 / Q000378:metabolism*; D045744:Cell Line, Tumor; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics* / Q000378:metabolism; D004249:DNA Damage; D000090205:DNA Methyltransferase 3A; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D034622:RNA Interference; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: C000717967:DNMT3A protein, human; C489427:MYC protein, human; D035683:MicroRNAs; C538984:Mirn182 microRNA, human; D016271:Proto-Oncogene Proteins c-myc; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9