Oncotarget

Research Papers:

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

Henan Zhao, Xiaotang Yu, Yanfang Ding, Jinyao Zhao, Guang Wang, Xian Wu, Jiyong Jiang, Chun Peng, Gordon Zhuo Guo _ and Shiying Cui

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2016; 7:53254-53268. https://doi.org/10.18632/oncotarget.10736

Metrics: PDF 1219 views  |   HTML 1797 views  |   ?  


Abstract

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

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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 10736