MiR-124-3p.1 Sensitizes Ovarian Cancer Cells to Mitochondrial Apoptosis Induced by Carboplatin.

Abstract

BackgroundCarboplatin is a platinum-based chemotherapeutic drug that is commonly used as a treatment for ovarian cancer. However, high doses and repeated use of carboplatin usually reduce the sensitivity of cancer cells to the drug. There is an urgent need to develop strategies to increase the sensitivity of ovarian cancer cells to carboplatin.Materials and MethodsQuantitative reverse-transcriptase real-time PCR was used to detect miR-124-3p.1 levels in ovarian cancer tissues and cell lines. Transfection with miR-124-3p.1 and caveolin-1 (CAV1) was used for gain-of-function experiments. Western blot and immunoprecipitation assays were performed to evaluate the expression and function of CAV1, AKT, Bad, and Bcl-xl. Flow cytometry analysis was used to measure the apoptosis rates of SKOV3 and A2780 cells.ResultsExpression levels of miR-124-3p.1 were decreased in ovarian cancer tissues and cell lines. Furthermore, overexpression of miR-124-3p.1 enhanced carboplatin-induced apoptotic cell death of ovarian cancer cell lines. Regarding the mechanism of this effect, we showed that CAV1 was the target of miR-124-3p.1 in ovarian cancer. Overexpression of miR-124-3p.1 suppressed the expression of CAV1, thereby reducing the activation of AKT and phosphorylation of Bad. As a result, the function of Bcl-xl was inhibited and carboplatin-induced mitochondrial apoptosis was enhanced.ConclusionmiR-124-3p.1 sensitizes carboplatin-induced mitochondrial apoptosis through suppression of CAV1 in ovarian cancer. Increasing miR-124-3p.1 expression may represent a novel strategy to improve carboplatin sensitivity in ovarian cancer.