TGF-β-induced miR10a/b expression promotes human glioma cell migration by targeting PTEN

Mol Med Rep. 2013 Dec;8(6):1741-6. doi: 10.3892/mmr.2013.1709. Epub 2013 Oct 1.

Abstract

Human gliomas are associated with high rates of morbidity and mortality. In the brain, increased mRNA levels of transforming growth factor β (TGF-β) correlate with the degree of malignancy of human gliomas. miR10a/10b expression has been demonstrated to be associated with TGF-β expression in brain tumors, and it is reported that TGF-β induces miR10 expression. Therefore, miR10a/10b expression may be induced by TGF-β expression and may be involved in the TGF-β-induced migration of brain tumor cells. The present study examined the expression of TGF-β and miR10a/10b in the tissues of 10 patients with brain tumors using quantitative PCR (qPCR), and the correlation between TGF-β and miR10a or miR10b expression was analyzed. Additionally, U251 and SHG-44 cells were treated with TGF-β and the expression of miR10a/10b was examined. Further, cell migration was analyzed following transfection of U251 cells with miR10a/10b and the association between miR10a/10b and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) was investigated. U251 cells were transfected with miR10a/10b inhibitors and a PTEN expression plasmid prior to TGF-β treatment and then cell migration was assessed. A significant correlation was identified between TGF-β and miR10a expression (r2=0.6936, P=0.007) and between TGF-β and miR10b expression (r2=0.5876, P=0.02) in the tissues of patients with brain tumors. The results also showed that TGF-β induces miR10a/10b expression and that TGF-β-induced miR10a/10b expression promotes cell migration through the suppression of PTEN. In conclusion, TGF-β-induced miR10a/10b promotes brain tumor migration. This study may provide a number of suggestions for the clinical treatment of brain tumors.

Keywords: miR10a/10b; TGF-β; cell migration; PTEN; brain tumor.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Base Sequence
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Movement* / drug effects
  • Cell Movement* / genetics
  • Gene Expression Regulation, Neoplastic* / drug effects
  • Glioma / genetics
  • Glioma / pathology*
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Molecular Sequence Data
  • PTEN Phosphohydrolase / metabolism*
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism*
  • Transforming Growth Factor beta / pharmacology

Substances

  • 3' Untranslated Regions
  • MIRN10 microRNA, human
  • MicroRNAs
  • Transforming Growth Factor beta
  • PTEN Phosphohydrolase
  • PTEN protein, human