MiR-770-5p inhibits cisplatin chemoresistance in human ovarian cancer by targeting ERCC2
Autor: | Yanfang Ding, Chun Peng, Xiaotang Yu, Gordon Zhuo Guo, Jiyong Jiang, Henan Zhao, Xian Wu, Shiying Cui, Jinyao Zhao, Guang Wang |
---|---|
Jazyk: | angličtina |
Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
DNA repair cisplatin Antineoplastic Agents Apoptosis Kaplan-Meier Estimate Bioinformatics chemoresisitance 03 medical and health sciences 0302 clinical medicine Cell Line Tumor microRNA medicine Gene silencing Humans miR-770-5p In Situ Hybridization Xeroderma Pigmentosum Group D Protein Cisplatin Ovarian Neoplasms business.industry Gene Expression Profiling Middle Aged medicine.disease Comet assay Gene Expression Regulation Neoplastic MicroRNAs 030104 developmental biology ovarian cancer Oncology Drug Resistance Neoplasm 030220 oncology & carcinogenesis Cancer research Biomarker (medicine) Female RNA Interference Ovarian cancer business ERCC2 medicine.drug Research Paper |
Zdroj: | Oncotarget |
ISSN: | 1949-2553 |
Popis: | 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. |
Databáze: | OpenAIRE |
Externí odkaz: |