Methylation-mediated silencing of microRNA-211 promotes cell growth and epithelial to mesenchymal transition through activation of the AKT/β-catenin pathway in GBM

Oncotarget. 2017 Apr 11;8(15):25167-25176. doi: 10.18632/oncotarget.15531.

Abstract

Aberrant expression of miR-211 has frequently been reported in cancer studies; however, its role in glioblastoma multiforme (GBM) has not been examined in detail. We investigated the function and the underlying mechanism of miR-211 in GBM. We revealed that miR-211 was downregulated in GBM tissues and cell lines. Restoration of miR-211 inhibited GBM cell growth and invasion both in vitro and in vivo. The epithelial to mesenchymal transition (EMT) phenotype was reversed when miR-211 expression was restored. HMGA2 was identified as a down-stream target of miR-211. MiR-211 had an inhibitory effect on AKT/β-catenin signaling, which was reversed by HMGA2 overexpression or miR-211 restoration. In addition, miR-211 was transcriptionally repressed by EZH2-induced H3K27 trimethylation and promoter methylation. Overall, our findings revealed miR-211 as a tumor suppressor in GBM and mir-211 may be a potential therapeutic target for GBM patients.

Keywords: EZH2; HMGA2; epithelial to mesenchymal transition; glioblastoma; miR-211.

MeSH terms

  • 3' Untranslated Regions
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation
  • DNA Methylation*
  • Epithelial-Mesenchymal Transition / genetics*
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing*
  • Glioblastoma / genetics
  • Glioblastoma / metabolism
  • HMGA2 Protein / genetics
  • Histones / metabolism
  • Humans
  • MicroRNAs / genetics*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • RNA Interference
  • Signal Transduction*
  • beta Catenin / metabolism*

Substances

  • 3' Untranslated Regions
  • HMGA2 Protein
  • Histones
  • MIRN211 microRNA, human
  • MicroRNAs
  • beta Catenin
  • Proto-Oncogene Proteins c-akt