title: MiR-770-5p inhibits cisplatin chemoresistance in human ovarian cancer by targeting ERCC2.
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.
authors.affiliation: Dalian Medical University, Dalian, China.
authors.forename: Henan
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Dalian Medical University, Dalian, China.
authors.forename: Xiaotang
authors.initials: X
authors.lastname: Yu
authors.affiliation: Dalian Medical University, Dalian, China.
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Dalian Medical University, Dalian, China.
authors.forename: Jinyao
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Dalian Medical University, Dalian, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Dalian Medical University, Dalian, China.
authors.forename: Xian
authors.initials: X
authors.lastname: Wu
authors.affiliation: Obstetrics and Gynecology Hospital, Dalian, China.
authors.forename: Jiyong
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Biology, York University, Toronto, Canada.
authors.forename: Chun
authors.initials: C
authors.lastname: Peng
authors.affiliation: Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Gordon Zhuo
authors.initials: GZ
authors.lastname: Guo
authors.affiliation: Dalian Medical University, Dalian, China.
authors.forename: Shiying
authors.initials: S
authors.lastname: Cui
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017403:In Situ Hybridization; D053208:Kaplan-Meier Estimate; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C000613306:MIRN7977 microRNA, human; D035683:MicroRNAs; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human; D002945:Cisplatin
keywords: ERCC2; chemoresisitance; cisplatin; miR-770-5p; ovarian cancer