Deregulation of miR-128 in Ovarian Cancer Promotes Cisplatin Resistance

作者：Li, Bing; Chen, Hong; Wu, Nan; Zhang, Wen-Jing; Shang, Li-Xin^*

来源：International Journal of Gynecological Cancer, 2014, 24(8): 1381-1388.

DOI：10.1097/IGC.0000000000000252

• miR-128
• Cisplatin
• Epithelial ovarian cancer
• ABCC5
• Bmi-1

Objective: Platinum-based chemotherapy is the standard treatment in advanced ovarian cancer, but most patients will relapse with drug-resistant disease. MicroRNAs have been demonstrated to function in chemoresistance in cancers. In this study, we focused on the role of miR-128 in cisplatin-resistant ovarian cancer.
Materials and Methods: The expression of miR-128 RNA and its targeted genes, the polycomb ring finger oncogene Bmi-1 and ATP-binding cassette subfamily C member 5 (ABCC5), were investigated in the epithelial ovarian cancer cells and ovarian carcinomas.
Results: miR-128 expression was significantly reduced in the cisplatin-resistant human epithelial ovarian cancer cell line SKOV3/CP compared with parental SKOV3 cells and decreased upon treatment with cisplatin in a concentration-dependent manner in SKOV3, OVCAR3, and PEO14 cells. Overexpression of miR-128 resensitized SKOV3/CP cells to cisplatin and reduced the expression of cisplatin-resistant-related proteins ABCC5 and Bmi-1, whereas miR-128 inhibitors increased cisplatin resistance in SKOV3 cells. Cisplatin combined with miR-128 agomirs inhibited the growth of SKOV3/CP xenograft tumors more effectively than cisplatin alone. Diminished expression of ABCC5 and Bmi-1 and higher cisplatin concentrations were observed in tumor tissue of mice treated with miR-128 agomirs in addition to cisplatin.
Conclusions: Taken together, our findings suggest that miR-128 may act as a promising therapeutic target for improvement of tumor sensitivity to cisplatin.

• 出版日期2014-10
• 单位中国人民解放军陆军总医院