MicroRNA-34a targets notch1 and inhibits cell proliferation in glioblastoma multiforme

Cancer Biol Ther. 2011 Sep 15;12(6):477-83. doi: 10.4161/cbt.12.6.16300. Epub 2011 Sep 15.

Abstract

Aberrant expression of microRNAs (miRNAs) has been implicated in cancer initiation and progression. In this study, we found that microRNA-34a (miR-34a) is significantly downregulated in glioblastoma multiforme (GBM) specimens compared with normal brain tissues. Growth curve and colony formation assays revealed that miR-34a suppresses proliferation of U373MG and SHG44 glioblastoma cells. Overexpression of miR-34a could induce apoptosis of glioblastoma cells. Also, we identified notch1 as a direct target gene of miR-34a. Knockdown of notch1 showed similar cellular functions as overexpression of miR-34a both in vitro and in vivo. Collectively, our findings show that miR-34a is downregulated in GBM cells and inhibits GBM growth by targeting notch1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Cell Line, Tumor
  • Cell Proliferation*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genes, Reporter
  • Glioblastoma / genetics*
  • Glioblastoma / metabolism
  • Humans
  • Luciferases, Renilla / biosynthesis
  • Luciferases, Renilla / genetics
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Neoplasm Transplantation
  • RNA Interference
  • Receptor, Notch1 / genetics*
  • Receptor, Notch1 / metabolism
  • Transcription, Genetic

Substances

  • 3' Untranslated Regions
  • MIRN34 microRNA, human
  • MicroRNAs
  • NOTCH1 protein, human
  • Receptor, Notch1
  • Luciferases, Renilla