MicroRNA-365 inhibits proliferation, migration and invasion of glioma by targeting PIK3R3

Abstract

A growing body of evidence suggests that microRNA-365 (miR-365) played crucial role in the initiation and development of many types of cancers. However, the biological role of miR-365 in human glioma remains unclear. Herein, the aims of this study were to investigate the role and underlying mechanisms of miR-365 in glioma by a series of in vitro and in vivo experiments. We found that miR-365 was strongly downregulated in malignant glioma tissues and cell lines. Restoration of the expression of miR-365 in glioma cells significantly inhibited cell proliferation, migration and invasion in vitro and tumor growth in vivo. Notably, phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3) was proved to be a direct target of miR-365 in glioma cells, and its mRNA expression was inversely correlated with miR-365 expression in clinical glioma tissues. PIK3R3 overexpression in miR-365 expressing cells could rescue proliferation, migration and invasion inhibition of miR-365. In addition, miR-365 was able to inhibit the phosphorylation of AKT and mTOR in vitro and in vivo, which are key participants in the AKT/mTOR pathway. These results suggest that miR-365 functioned as a tumor suppressor in glioma by targeting PIK3R3, suggesting that miR-365 has potential as therapeutic targets for glioma.