miR-142 inhibits the migration and invasion of glioma by targeting Rac1

Oncol Rep. 2017 Sep;38(3):1543-1550. doi: 10.3892/or.2017.5816. Epub 2017 Jul 13.

Abstract

Increasing evidence has shown that aberrant microRNAs (miRNAs) are implicated in tumorigenesis and tumor progression by regulating oncogenes or tumor suppressors. Dysregulation of miR-142 has been reported in multiple tumors. However, its clinical roles and underlying mechanism in glioma remain to be elucidated. In the present study, we found that the expression of miR-142 was significantly downregulated in both glioma tissues and cell lines by qRT-PCR. Clinical analysis revealed that decreased miR-142 was markedly associated with advanced World Health Organization (WHO) grade. Moreover, we disclosed that miR-142 was a novel independent prognostic marker in the prediction of the 5-year survival of glioma patients. The ectopic overexpression of miR-142 inhibited cell migration, invasion and invasion‑related gene expression. Notably, miR-142 modulated Rac1 by directly binding to its 3'-untranslated (3'-UTR) region, leading to the suppression of the expression of matrix metalloproteinases (MMPs). In glioma clinical samples, miR-142 was inversely correlated with Rac1 expression, and played positive roles in glioma migration and invasion. Alteration of Rac1 expression at least partially abolished the migration, invasion and MMP expression of miR-142 in glioma cells. In the present study, we identified Rac1 as a functional target of miR-142 in glioma. In conclusion, our data indicated that miR-142 inhibited the migration, invasion and MMP expression of glioma by targeting Rac1, and may represent a novel potential therapeutic target and prognostic marker for glioma.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Biomarkers, Tumor / genetics
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Cell Proliferation / genetics
  • Cell Transformation, Neoplastic / genetics
  • Down-Regulation / genetics
  • Gene Expression Regulation, Neoplastic / genetics*
  • Glioma / genetics*
  • Glioma / pathology
  • Humans
  • Matrix Metalloproteinases / genetics
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics*
  • Neoplasm Invasiveness / pathology
  • rac1 GTP-Binding Protein / genetics*

Substances

  • 3' Untranslated Regions
  • Biomarkers, Tumor
  • MIRN142 microRNA, human
  • MicroRNAs
  • RAC1 protein, human
  • Matrix Metalloproteinases
  • rac1 GTP-Binding Protein