miR-218 inhibits the invasive ability of glioma cells by direct downregulation of IKK-β

Aberrant activation of nuclear factor-kappa B (NF-kappa B) pathway has been proven to play important roles in the development and progression of cancers. Activation of NF-kappa B via the classical pathway is modulated by I kappa Bs kinase (IKK-beta). However, the mechanism underlying the epigenetic regulation of IKK-beta/NF-kappa B pathway remains largely unknown. In this study, we found that the expression level of miR-218 was markedly downregulated in glioma cell lines and in human primary glioma tissues. Upregulation of miR-218 dramatically reduced the migratory speed and invasive ability of glioma cells. Furthermore, we showed that ectopically expressing miR-218 in glioma cells resulted in downregulation of matrix metalloproteinase-9 (MMP-9) and reduction in NF-kappa B transactivity at a transcriptional level, but inhibition of miR-218 enhanced the expression of MMP-9 and transcriptional activity of NF-kappa B. Moreover, we showed that miR-218 inactivated the NF-kappa B pathway through downregulating IKK-beta expression by directly targeting the 3'-untranslated region (3'-UTR) of IKK-beta. Taken together, our results suggest that miR-218 plays an important role in preventing the invasiveness of glioma cells, and our results present a novel mechanism of miRNA-mediated direct suppression of IKK-beta/NF-kappa B pathway in gliomas. (C) 2010 Elsevier Inc. All rights reserved.