MiR-770-5p inhibits cisplatin chemoresistance in human ovarian cancer by targeting ERCC2
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Henan Zhao1, Xiaotang Yu1, Yanfang Ding1, Jinyao Zhao1, Guang Wang1, Xian Wu1, Jiyong Jiang2, Chun Peng3, Gordon Zhuo Guo4, Shiying Cui1
1Dalian Medical University, Dalian, China
2Obstetrics and Gynecology Hospital, Dalian, China
3Department of Biology, York University, Toronto, Canada
4Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, IN, USA
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
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.
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