title: miR-125b confers resistance of ovarian cancer cells to cisplatin by targeting pro-apoptotic Bcl-2 antagonist killer 1.
abstract: Chemotherapy is the preferred therapeutic approach for advanced ovarian cancer, but a successful long-term treatment is prevented by the development of drug resistance. Recent works have underlined the involvement of non-coding RNAs, microRNAs (miRNAs) in cancer development, with several conjectures regarding their possible involvement in the evolution of drug resistance. This study is to investigate the promoting effects and mechanism of miR-125b involved in the development of chemoresistance in ovarian cancer. The different expression of miR-125b in cisplatin-sensitive ovarian cancer cell line (OV2008) and its resistant variant (C13*) was identified by real-time PCR. An in vitro cytotoxicity assay and apoptosis assay using CCK-8 assay and flow cytometry, were carried out to detect the effect of miR-125b and Bak1 on cisplatin resistance of cells. Real-time PCR, Western blotting and luciferase reporter assay were used to detect whether Bak1 is a target of miR-125b. As compared with OV2008 cells, the expression levels of miR-125b in C13* cells were increased. It was found that the up-regulation of microRNA-125b caused a marked inhibition of cisplatin-induced cytotoxicity and apoptosis and a subsequent increase in the resistance to cisplatin in OV2008 and C13* cells. Moreover, Bak1 was a direct target of miR-125b, and down-regulation of Bak1 suppressed cisplatin-induced apoptosis and led to an increased resistance to cisplatin. Our study indicates that miR-125b has a significantly promoting effect on chemoresistance of C13* cells and up-regulation of miR-125b expression contributes to cisplatin resistance through suppression of Bak1 expression. This finding has important implications in the development of targeted therapeutics for overcoming cisplatin resistance in ovarian cancer.
authors.affiliation: Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.|Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, 200040, China.
authors.forename: Fanfei
authors.initials: F
authors.lastname: Kong
authors.affiliation: Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Chaoyang
authors.initials: C
authors.lastname: Sun
authors.affiliation: Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Zhongxian
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, 200040, China.
authors.forename: Lingfei
authors.initials: L
authors.lastname: Han
authors.affiliation: Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Danhui
authors.initials: D
authors.lastname: Weng
authors.affiliation: Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Yunping
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. gumpc@126.com.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000235:genetics*
chemical_list: C531888:MIRN125 microRNA, human; D035683:MicroRNAs; D050998:bcl-2 Homologous Antagonist-Killer Protein; D002945:Cisplatin