miR-182-5p enhances cisplatin resistance in epithelial ovarian cancer by downregulating GRB2

Objective: Epithelial ovarian cancer (EOC) patients often experience cisplatin resistance. This study analysed the miR-182 level in EOC patients, and explored the association between miR-182 with chemoresistance in EOC. Methods: Using qRT-PCR, the miR-182-5p levels in EOC were determined. miR-182-5p and its associations with the clinicopathological characteristics and overall survival of EOC patients were analysed. A2780/DDP cells and A2780 cells were transfected with miR-182-5p mimics or inhibitor. Then, using a CCK8 assay, cell viabilities were assessed. To determine if GRB2 is a bona fide miR-182-5p target, a dual luciferase reporter assay was carried out. Then, the cell viability in A2780/DDP cells overexpressing GRB2 was determined. Results: Compared with adjacent normal tissues, the miR-182-5p was significantly upregulated in EOC tissues. High levels of miR-182-5p were associated with frequent platinum resistance and poor overall survival in EOC patients. Upregulation of miR-182-5p by its mimics significantly enhanced the cisplatin resistance of A2780 cells. Conversely, miR-182-5p inhibitors significantly enhanced the cisplatin sensitivity of A2780/DDP cells. GRB2 was confirmed as a bona fide miR-182-5p target in EOC. In GRB2-overexpressing EOC cells, cisplatin sensitivity was significantly enhanced. Conclusions: miR-182-5p enhanced the cisplatin resistance of EOC cells by downregulating GRB2, which is a novel target for predicting the prognosis and improving the treatment of EOC.

Epithelial ovarian cancer; miR-182; GRB2; Cisplatin; Chemoresistance

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