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MiR-770-5p inhibits cisplatin chemoresistance in human ovarian cancer by targeting ERCC2
Author(s) -
Henan Zhao,
Xiaotang Yu,
Yanfang Ding,
Jinyao Zhao,
Guang Wang,
Xian Wu,
Jiyong Jiang,
Chun Peng,
Gordon Guo,
Shiying Cui
Publication year - 2016
Publication title -
oncotarget
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.373
H-Index - 127
ISSN - 1949-2553
DOI - 10.18632/oncotarget.10736
Subject(s) - cisplatin , ercc2 , medicine , ovarian cancer , cancer research , microrna , oncology , gene silencing , olaparib , chemotherapy , ercc1 , cancer , dna repair , nucleotide excision repair , biology , gene , genetics , poly adp ribose polymerase , polymerase
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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