MiR125a-5p acting as a novel Gab2 suppressor inhibits invasion of glioma.

Poor prognosis of glioma is due to the characteristics of high invasiveness. Recently, it was demonstrated that Gab2 was over-expressed and related to cellular migration and invasion in glioma, however, the mechanisms of regulation are still unknown. A better understanding of molecular events key to the carcinogenesis and tumor progression may facilitate development of new therapeutic targets and anti-glioma strategies. This study is the first to focus on miR125a-5p, which was predicted to regulate Gab2 with directly targeting the 3' un-translated region (3'UTR) of Gab2 and could inhibit migration and invasion of glioma cells by mediating Gab2 to affect cytoskeleton rearrangement and matrix metalloproteinases expression. Interestingly, further evaluation revealed that the miR125a-5p promoter was hypermethylated and that attenuating promoter methylation was sufficient to up-regulate miR125a-5p expression in glioma cells. Additionally, we reported that miR125a-5p was down-regulated in glioma as well as statistical analysis suggested that its expression level correlated with the World Health Organization grades of glioma (P < 0.05) and that patients with a low miR125a-5p level exhibited shorter survival time (P < 0.05). Taken together, these results reveal that miR125a-5p represents potential therapeutic targets in glioma by modulating Gab2.