TGF-β induced miR-132 enhances the activation of TGF-β signaling through inhibiting SMAD7 expression in glioma cells

Biochem Biophys Res Commun. 2015 Jul 31;463(3):187-92. doi: 10.1016/j.bbrc.2015.05.001. Epub 2015 May 15.

Abstract

Transforming growth factors β (TGF-β) pathway has been proven to play important roles in oncogenesis and angiogenesis of gliomas. MiR-132 might be related to TGF-β signaling pathway and high miR-132 expression was reported to be a biomarker of poor prognosis in patients diagnosed with glioma. However, the expression regulation way involved in TGF-β pathway and clinical significance of miR-132 have not been investigated in glioma cells. Here we reported that the mRNA level of miR-132 and TGF-β concentration were both increased in patients with brain glioma. Correlation analysis revealed that TGF-β concentration was positively correlated with mRNA level of miR-132. In addition, the mRNA level of miR-132 was up-regulated by TGF-β in a concentration-dependent and time-dependent manner. Furthermore, we found that miR-132 was involved in modulation of the TGF-β signaling pathway and down-regulation of SMAD7 expression by directly targeting the SMAD7 3'-UTR. MiR-132 was negatively correlated with SMAD7 in patients with brain glioma. Taken together, our results suggest that miR-132 could be stimulated by TGF-β and might enhance the activation of TGF-β signaling through inhibiting SMAD7 expression in glioma cells. These findings contribute to a better understanding of the mechanism of the activation of TGF-β signaling by miR-132.

Keywords: Glioma cells; SMAD2; SMAD7; Transforming growth factors β; miR-132.

MeSH terms

  • Brain / metabolism
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / metabolism
  • Cell Line
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Glioma / genetics*
  • Glioma / metabolism
  • Humans
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Signal Transduction
  • Smad7 Protein / genetics*
  • Transforming Growth Factor beta / metabolism*

Substances

  • MIRN132 microRNA, human
  • MicroRNAs
  • Smad7 Protein
  • Transforming Growth Factor beta