Identification of MMP-9 specific microRNA expression profile as potential targets of anti-invasion therapy in glioblastoma multiforme

Brain Res. 2011 Sep 9:1411:108-15. doi: 10.1016/j.brainres.2011.07.002. Epub 2011 Jul 13.

Abstract

The poor prognosis of glioblastoma multiforme (GBM) is largely attributed to their highly invasive nature and MMP-9 plays a pivotal role in regulating invasiveness of malignant glioma cells. MicroRNAs (miRNAs) are small non-coding RNAs that have been shown to regulate a wide range of biological processes via targeting messenger RNA. Previous reports have shown many oncogenes regulate survival and invasion via targeting MMP-9 in GBM. But no literature indicates that miRNAs regulate glioma cell invasion through targeting MMP-9. Here, we show MMP-9 overexpression conferred a poor prognosis in 163 GBM patients. Furthermore, MMP-9 specific miRNA expression profile (14 positively and 31 negatively correlated miRNAs with MMP-9) was established via miRNA microarrays in 60 GBM samples. Among them, two miRNAs: miR-885-5p and miR-491-5p, were chosen for functional validation for their high positive correlation with MMP-9 expression. And upregulation of miR-885-5p and miR-491-5p were demonstrated to reduce the levels of MMP-9 expression and inhibit cellular invasion in U251 and U87 glioma cells. Furthermore, we found that miR-491-5p suppressed glioma cell invasion via targeting MMP-9 directly. To our knowledge, this is the first study to identify the MMP-9 specific microRNA signature which may provide potential targets for anti-invasion therapy in GBM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Blotting, Western
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / enzymology*
  • Cell Line, Tumor
  • Disease-Free Survival
  • Down-Regulation / drug effects
  • Genes, Reporter
  • Glioblastoma / drug therapy*
  • Glioblastoma / enzymology*
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Luciferases / genetics
  • Matrix Metalloproteinase 9 / biosynthesis*
  • Matrix Metalloproteinase 9 / genetics
  • MicroRNAs / biosynthesis*
  • MicroRNAs / drug effects*
  • MicroRNAs / genetics
  • Microarray Analysis
  • Neoplasm Invasiveness / pathology
  • Oligonucleotides / genetics
  • Prognosis
  • RNA, Neoplasm / biosynthesis
  • RNA, Neoplasm / isolation & purification
  • Survival Analysis
  • Transfection

Substances

  • Antineoplastic Agents
  • MicroRNAs
  • Oligonucleotides
  • RNA, Neoplasm
  • Luciferases
  • Matrix Metalloproteinase 9