MiR-221/222 promote human glioma cell invasion and angiogenesis by targeting TIMP2

Tumour Biol. 2015 May;36(5):3763-73. doi: 10.1007/s13277-014-3017-3. Epub 2015 Mar 4.

Abstract

miR-221/222 are two highly homologous microRNAs that are frequently upregulated in solid tumors. However, the effects of miR-221/222 in malignant gliomas have not been investigated thoroughly. In this study, we found that miR-221/222 were significantly upregulated in human glioma samples and glioma cell lines. Both gain- and loss-of-function studies showed that miR-221/222 regulate cell proliferation, the cell cycle and apoptosis, in addition to, invasion, metastasis, and angiogenesis in glioma cell lines. Subsequent investigations revealed that TIMP2 is a direct target of miR-221/222, and overexpression of TIMP2 reduced the miR-221/222-mediated invasion, metastasis, and angiogenesis of glioma cells. Taken together, our results suggest that the suppression of miR-221/222 may be a feasible approach for inhibiting the malignant behaviors of glioma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Glioma / genetics*
  • Glioma / pathology
  • Humans
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Neoplasm Invasiveness / genetics
  • Neoplasm Metastasis
  • Neovascularization, Pathologic / genetics
  • Tissue Inhibitor of Metalloproteinase-2 / biosynthesis*
  • Tissue Inhibitor of Metalloproteinase-2 / genetics

Substances

  • MIRN221 microRNA, human
  • MIRN222 microRNA, human
  • MicroRNAs
  • TIMP2 protein, human
  • Tissue Inhibitor of Metalloproteinase-2