MiR-770-5p inhibits cisplatin chemoresistance in human ovarian cancer by targeting ERCC2

Abstract

// Henan Zhao 1 , Xiaotang Yu 1 , Yanfang Ding 1 , Jinyao Zhao 1 , Guang Wang 1 , Xian Wu 1 , Jiyong Jiang 2 , Chun Peng 3 , Gordon Zhuo Guo 4 , Shiying Cui 1 1 Dalian Medical University, Dalian, China 2 Obstetrics and Gynecology Hospital, Dalian, China 3 Department of Biology, York University, Toronto, Canada 4 Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, IN, USA Correspondence to: Shiying Cui, email: scui2003@dlmedu.edu.cn , 2501532244@qq.com Gordon Zhuo Guo, email: gguo1@IUhealth.org Keywords: ovarian cancer, cisplatin, chemoresisitance, miR-770-5p, ERCC2 Received: January 02, 2016      Accepted: July 06, 2016      Published: July 20, 2016 ABSTRACT In this study, we examined the role of the miRNA miR-770-5p in cisplatin chemotherapy resistance in ovarian cancer (OVC) patients. miR-770-5p expression was reduced in platinum-resistant patients. Using a 6.128-fold in expression as the cutoff value, miR-770-5p expression served as a prognostic biomarker and predicted the response to cisplatin treatment and survival among OVC patients. Overexpression of miR-770-5p in vitro reduced survival in chemoresistant cell lines after cisplatin treatment. ERCC2, a target gene of miR-770-5p that participates in the NER system, was negatively regulated by miR-770-5p. siRNA-mediated silencing of ERCC2 reversed the inhibition of apoptosis resulting from miR-770-5p downreglation in A2780S cells. A comet assay confirmed that this restoration of cisplatin chemosensitivity was due to the inhibition of DNA repair. These findings suggest that endogenous miR-770-5p may function as an anti-oncogene and promote chemosensitivity in OVC, at least in part by downregulating ERCC2. miR-770-5p may therefore be a useful biomarker for predicting chemosensitivity to cisplatin in OVC patients and improve the selection of effective, more personalized, treatment strategies.