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

Mol Carcinog. 2016 Jan;55(1):40-51. doi: 10.1002/mc.22256. Epub 2015 Jan 18.

Abstract

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.

Keywords: MiR125a-5p; glioma; invasion; methylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / chemistry
  • Actins / metabolism
  • Adaptor Proteins, Signal Transducing / chemistry
  • Adaptor Proteins, Signal Transducing / genetics*
  • Adult
  • Aged
  • Base Sequence
  • Binding Sites
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / mortality
  • Brain Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Transformation, Neoplastic / genetics
  • CpG Islands
  • DNA Methylation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glioma / genetics*
  • Glioma / mortality
  • Glioma / pathology*
  • Humans
  • Insulin-Like Growth Factor I / metabolism
  • Insulin-Like Growth Factor I / pharmacology
  • Male
  • MicroRNAs / chemistry
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Invasiveness
  • Prognosis
  • Protein Multimerization / drug effects
  • RNA Interference
  • RNA, Messenger / chemistry
  • RNA, Messenger / genetics
  • Young Adult

Substances

  • Actins
  • Adaptor Proteins, Signal Transducing
  • GAB2 protein, human
  • MIRN125 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • Insulin-Like Growth Factor I