MiR-26a enhances the radiosensitivity of glioblastoma multiforme cells through targeting of ataxia-telangiectasia mutated

Exp Cell Res. 2014 Jan 15;320(2):200-8. doi: 10.1016/j.yexcr.2013.10.020. Epub 2013 Nov 5.

Abstract

Glioblastoma multiforme (GBM) is notoriously resistant to radiation, and consequently, new radiosensitizers are urgently needed. MicroRNAs are a class of endogenous gene modulators with emerging roles in DNA repair. We found that overexpression of miR-26a can enhance radiosensitivity and reduce the DNA repair ability of U87 cells. However, knockdown miR-26a in U87 cells could act the converse manner. Mechanistically, this effect is mediated by direct targeting of miR-26a to the 3'UTR of ATM, which leads to reduced ATM levels and consequent inhibition of the homologous recombination repair pathway. These results suggest that miR-26a may act as a new radiosensitizer of GBM.

Keywords: ATM; DNA repair; Glioblastoma multiforme; MiR-26a.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ataxia Telangiectasia Mutated Proteins / genetics*
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / radiotherapy*
  • DNA Repair / genetics
  • DNA Repair / radiation effects
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Gene Targeting
  • Glioblastoma / genetics*
  • Glioblastoma / radiotherapy*
  • Humans
  • Mice
  • Mice, Nude
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / physiology*
  • Radiation Tolerance / genetics*
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • MIRN26A microRNA, human
  • MicroRNAs
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins