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.
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Authors | Henan Zhao, Xiaotang Yu, Yanfang Ding, Jinyao Zhao, Guang Wang, Xian Wu, Jiyong Jiang, Chun Peng, Gordon Zhuo Guo, Shiying Cui |
Journal | Oncotarget
(Oncotarget)
Vol. 7
Issue 33
Pg. 53254-53268
(Aug 16 2016)
ISSN: 1949-2553 [Electronic] United States |
PMID | 27449101
(Publication Type: Journal Article)
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Chemical References |
- Antineoplastic Agents
- MIRN7977 microRNA, human
- MicroRNAs
- Xeroderma Pigmentosum Group D Protein
- ERCC2 protein, human
- Cisplatin
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Topics |
- Antineoplastic Agents
(therapeutic use)
- Apoptosis
(drug effects, 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, genetics, metabolism)
- RNA Interference
- Xeroderma Pigmentosum Group D Protein
(genetics, metabolism)
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