MiRNA-125a-5p inhibits glioblastoma cell proliferation and promotes cell differentiation by targeting TAZ

Biochem Biophys Res Commun. 2015 Feb 6;457(2):171-6. doi: 10.1016/j.bbrc.2014.12.078. Epub 2014 Dec 24.

Abstract

Glioblastoma (GBM) is the most lethal brain tumor due to the resistance to conventional therapies, such as radiotherapy and chemotherapy. TAZ, an important mediator of the Hippo pathway, was found to be up-regulated in diverse cancers, including in GBM, and plays important roles in tumor initiation and progression. However, little is known about the regulation of TAZ expression in tumors. In this study, we found that miR-125a-5p is an important regulator of TAZ in glioma cells by directly targeting the TAZ 3' UTR. MiR-125a-5p levels are inversely correlated with that of TAZ in normal astrocytes and a panel of glioma cell lines. MiR-125a-5p represses the expression of TAZ target genes, including CTGF and survivin, and inhibits cell proliferation and induces the differentiation of GBM cells; whereas over-expression of TAZ rescues the effects of miR-125a-5p. This study revealed a mechanism for TAZ deregulation in glioma cells, and also demonstrated a tumor suppressor role of miR-125a-5p in glioblastoma cells.

Keywords: Cell differentiation; Glioblastoma; TAZ; miR-125a-5p.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Base Sequence
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / pathology*
  • Cell Differentiation* / genetics
  • Cell Line, Tumor
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Genes, Neoplasm
  • Glioblastoma / genetics*
  • Glioblastoma / pathology*
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Molecular Sequence Data
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Trans-Activators
  • Transcription Factors
  • Transcriptional Coactivator with PDZ-Binding Motif Proteins

Substances

  • 3' Untranslated Regions
  • Intracellular Signaling Peptides and Proteins
  • MIRN125 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • Trans-Activators
  • Transcription Factors
  • Transcriptional Coactivator with PDZ-Binding Motif Proteins
  • WWTR1 protein, human