Journal
BRAIN RESEARCH
Volume 1411, Issue -, Pages 108-115Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.brainres.2011.07.002
Keywords
Glioma; MicroRNA; Invasion; MMP-9; miR-885-5p; miR-491-5p
Categories
Funding
- National Key Project of Science and Technology Supporting Programs of China [2007BAI05B08]
- National Natural Science Foundation of China [30772238, 30730035]
- National Basic Research Program of China [2010CB529406]
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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. (C) 2011 Elsevier B.V. All rights reserved.
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