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Item MiR-770-5p inhibits cisplatin chemoresistance in human ovarian cancer by targeting ERCC2(Impact Journals, 2016-08-16) Zhao, Henan; Yu, Xiaotang; Ding, Yanfang; Zhao, Jinyao; Wang, Guang; Wu, Xian; Jiang, Jiyong; Peng, Chun; Guo, Gordon Zhuo; Cui, Shiying; Department of Radiation Oncology, IU School of MedicineIn 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.Item Testing the metal of ERCC2 in predicting the response to platinum-based therapy(American Association for Cancer Research, 2014-10) Turchi, John J.; Woods, Derek S.; VanderVere-Carozza, Pamela; Department of Medicine, IU School of MedicineDNA repair has been shown to affect the cellular response to platinum-based therapy in a variety of cancers; however, translating this knowledge to the clinic has proven difficult and yielded mixed results. In this issue of Cancer Discovery, Van Allen and colleagues have analyzed responders and nonresponders to neoadjuvant platinum-based therapy with locally advanced urothelial cancer and identified a series of mutations in the nucleotide excision repair (NER) gene ERCC2 that correlate with the response to platinum-based therapy. This work provides evidence that defects in NER can be exploited to maximize the efficacy of conventional platinum-based chemotherapy.