Microrna-149 Inhibits Proliferation and Invasion of Glioma Cells via Blockade of Akt1 Signaling

Abstract

MicroRNAs (miRNAs) play important roles in the regulation of gene expressions. Aberrant expression of miRNAs is implicated in a variety of biological and pathological processes, including the tumorigenesis of glioma (GM). Though the molecular mechanisms of protein kinase B (AKT) survival signal have been comprehensively explored, the role of miR-149 in glioblastoma (GBM) and its regulation on AKT signaling have not yet been ascertained. The present study aimed to elucidate the role and molecular mechanisms of miR-149 in U251 GM cells. Using a gain-of-function approach, we investigated the effects of lentivirus-mediated overexpression of miR-149 on the expression of phosphated-AKT1 (p-AKT1), proliferating cell nuclear antigen (PCNA), matrix metallopeptidase-2 (MMP-2) and CyclinD1 in U251 cells and nude mice subcutaneous xenograft tumors by Real-time PCR, Western blot and immunohistochemical assays. Proliferative activities indicated by MTT assay, invasive potential by Transwell and cycle distribution by flow cytometry were carried out for functional analysis of U251 cells after infection with miR-149 mimic. As a consequence, miR-149 inhibited the expression of p-AKT1, PCNA, CyclinD1 and MMP-2, reduced the proliferative activities and invasive potential, and induced cycle arrest in G0/G1 phase in U251 cells. In conclusion, our findings show that miR-149 as tumor suppressor may be involved in the proliferation and invasion of GM cells via blockade of the AKT1 signaling, and be considered as a candidate target for the treatment of cancer.