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

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.

Urinary and Blood MicroRNA-126 and -770 are Potential Noninvasive Biomarker Candidates for Diabetic Nephropathy: a Meta-Analysis

“…Based on its targeting of the nucleotide excision repair enzyme ERCC2 in chemoresistant ovarian cancer [40, 41] and its sequestration by the upregulated lncRNA PCGEM1 in osteoarthritic synoviocytes [42], one could hypothesize an overall role in apoptosis. Further study is needed to elucidate the molecular mechanisms of miR-770 action in relation with DN.…”

Core fucosylation of copper transporter 1 plays a crucial role in cisplatin‐resistance of epithelial ovarian cancer by regulating drug uptake

“…During the therapy process of EOC, about 90% of patients exhibited chemo resistance . To investigate the role of core fucosylation in the cDDP‐resistance of EOC, we evaluated the sera of 21 patients, who had received primary surgery.…”

“…Epithelial ovarian cancer (EOC) is the most lethal female genital tract cancer in the world . The standard therapy scheme for the initial management of ovary cancer is based on cytoreductive surgery, followed by primary chemotherapy with a platinum‐based regimen . The first‐line chemotherapy with platinum and paclitaxel yields a response rate of more than 80%.…”

“…The first‐line chemotherapy with platinum and paclitaxel yields a response rate of more than 80%. Despite an initial high response rate, EOC has a poor prognosis due to the high proportion of chemo resistance (approximately 90%), and the 5‐year survival rate for advanced ovarian cancer is less than 30%. Reduced cellular accumulation of platinum‐based drugs, enhanced detoxification capability, aberrant apoptosis pathways, and increased DNA repair ability from DNA damage are associated with the chemo resistance, however, the precise mechanisms of how EOC cells achieve resistance to platinum drugs have not been fully identified.…”

MicroRNAs in gynecological cancers: Small molecules with big implications

“…let-7e [258], miR-29 [259], miR-128 [260], miR-136 [261], miR-155 [262], miR-199a [263], miR-216b [264], miR-449a [265], miR-489 [266], miR-595 [267], miR-634 [268] and miR-770 [269] inversely correlate with cisplatin resistance in OC while miR-218 [270, 271] increases sensitivity to cisplatin in CC cells. miR-21 [272, 273], miR-125b [274], miR-214 [160], miR-224 [275], miR-376c [276] and miR-509 [277] induce cisplatin resistance in OC.…”