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

Oncotarget. 2016 Aug 16;7(33):53254-53268. doi: 10.18632/oncotarget.10736.

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.

Keywords: ERCC2; chemoresisitance; cisplatin; miR-770-5p; ovarian cancer.

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cisplatin / therapeutic use*
  • Drug Resistance, Neoplasm / genetics*
  • Female
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • In Situ Hybridization
  • Kaplan-Meier Estimate
  • MicroRNAs / genetics*
  • Middle Aged
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism
  • RNA Interference
  • Xeroderma Pigmentosum Group D Protein / genetics*
  • Xeroderma Pigmentosum Group D Protein / metabolism

Substances

  • Antineoplastic Agents
  • MIRN7977 microRNA, human
  • MicroRNAs
  • Xeroderma Pigmentosum Group D Protein
  • ERCC2 protein, human
  • Cisplatin