MicroRNA-1179 regulates proliferation and chemosensitivity of human ovarian cancer cells by targeting the PTEN-mediated PI3K/AKT signaling pathway.

Abstract

IntroductionOwing to widespread roles of miRs, the dysregulation of their expression in human tissues has been linked with the development of several diseases such as cancer. The study was designed to investigate the role and therapeutic potential of miR-1179 in ovarian cancer.Material and methodsProliferation rate was monitored by MTT assay. Transfections were performed using Lipofectamine 2000 reagent. Cell cycle apoptosis was detected by AO/EB and annexin V/PI staining. Expressions analysis was carried out by qRT-PCR and western blotting. In vivo evaluation was carried out in xenografted mouse models.ResultsThe results revealed that miR-1179 is considerably upregulated in ovarian cancer cell lines. Inhibition of miR-1179 triggers decrease in the viability via initiation of apoptotic cell death of ovarian PA-1 cancer cells. TargetScan analysis showed PTEN to be the main target of miR-1179 in PA-1 cells. Exploration of PTEN expression in ovarian cancer cell lines revealed up to 9-fold downregulation of PTEN. However, inhibition of miR-1179 in PA-1 cells resulted in upregulation of PTEN expression. In addition, overexpression of PTEN caused a reduction of PA-1 cell viability via induction of apoptotic cell death. However, silencing of miR-1179 could rescue the effects of miR-1179 inhibition on the proliferation of miR-1179. The miR-1179 suppression was accompanied by a significant decline in phosphorylation of PI3K and AKT expression in the PA-1 cells. The in vivo study showed that miR-1179 suppression inhibits the xenografted tumor growth.ConclusionsThe results of this study indicate that miR-1179 may prove to be an important therapeutic target for ovarian cancer.