miR-125b Confers Resistance of Ovarian Cancer Cells to Cisplatin by Targeting Pro-apoptotic Bcl-2 Antagonist Killer 1

• Published in: Journal of Huazhong University of Science and Technology. Medical sciences Vol. 31; no. 4; pp. 543 - 549
• Main Author: 孔繁飞 孙朝阳 王中显 韩凌斐 翁丹卉 卢运萍 陈刚
• Format: Journal Article
• Language: English
• Published: Heidelberg Huazhong University of Science and Technology 01.08.2011
• Subjects: Apoptosis; Apoptosis - genetics; bcl-2 Homologous Antagonist-Killer Protein - genetics; Bcl-2 protein; Cell Line, Tumor; Chemoresistance; Chemotherapy; Cisplatin; Cisplatin - pharmacology; Cytotoxicity; Drug development; Drug resistance; Drug Resistance, Neoplasm - genetics; Evolution; Female; Flow cytometry; Humans; Medicine; Medicine & Public Health; MicroRNAs - genetics; MIR; miRNA; non-coding RNA; Ovarian cancer; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - genetics; Polymerase chain reaction; Tumor cell lines; Western blotting; Western印迹法; 卵巢癌; 受体拮抗剂; 细胞凋亡; 细胞株; 顺铂; miR-125b; Bak1; ovarian cancer; cisplatin resistance
• ISSN: 1672-0733; 1993-1352
• DOI: 10.1007/s11596-011-0487-z

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.