miR-383 inhibits ovarian cancer cell proliferation, invasion and aerobic glycolysis by targeting LDHA
Abstract:
MicroRNAs (miRNAs) are differentially expressed in various cancers and act as oncogenes or tumor suppressors. MiR-383 has been characterized as a cancer suppressor in several cancers. However, the exact expression patterns of miR-383 and the precise molecular mechanisms underlying its role in ovarian cancer have not been investigated thoroughly. In this study, we found that the expression of miR-383 was significantly downregulated in ovarian cancer tissues and ovarian cancer cell lines. Ectopic expression of miR-383 remarkably suppressed the ovarian cancer cell proliferation by enhancing cell apoptosis and significantly inhibited the invasion of ovarian cancer cells, while low expression of miR-383 exhibited the opposite effect. Bioinformatics analysis suggested LDHA as a novel target of miR-383, and miR-383 suppressed the expression level of LDHA mRNA by direct binding to its 3'-untranslated region (3'UTR). Expression of miR-383 was negatively correlated with LDHA in ovarian cancer tissues. In addition, modulation of miR-383 expression could affect the aerobic glycolysis in the ovarian cancer cells. Furthermore, Silencing of LDHA counteracted the effects of miR-383 suppression, while its overexpression reversed tumor inhibitory effects of miR-383. In conclusion, our study demonstrated that miR-383 regulated LDHA expression in ovarian cancer cells, thereby stunting glycolysis, cell proliferation and invasion.