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

Abstract

Aberrant activation of nuclear factor-kappa B (NF-κB) pathway has been proven to play important roles in the development and progression of cancers. Activation of NF-κB via the classical pathway is modulated by IκBs kinase (IKK-β). However, the mechanism underlying the epigenetic regulation of IKK-β/NF-κB 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-κB transactivity at a transcriptional level, but inhibition of miR-218 enhanced the expression of MMP-9 and transcriptional activity of NF-κB. Moreover, we showed that miR-218 inactivated the NF-κB pathway through downregulating IKK-β expression by directly targeting the 3'-untranslated region (3'-UTR) of IKK-β. 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-β/NF-κB pathway in gliomas.

• Authors: Libing Song, Quan Huang, Kun Chen, Liping Liu, Chuyong Lin, Ting Dai, Chunping Yu, Zhiqiang Wu, Jun Li
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 402 Issue 1 Pg. 135-40 (Nov 05 2010) ISSN: 1090-2104 [Electronic] United States
• PMID: 20933503 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier Inc. All rights reserved.

Chemical References

• MIRN218 microRNA, human
• MicroRNAs
• I-kappa B Kinase
• Matrix Metalloproteinase 9

Topics

• Base Sequence
• Cell Line, Tumor
• Down-Regulation
• Epigenomics
• Gene Expression Regulation, Neoplastic
• Glioma (genetics, pathology)
• Humans
• I-kappa B Kinase (genetics)
• Matrix Metalloproteinase 9 (genetics)
• MicroRNAs (genetics, metabolism)
• Molecular Sequence Data
• Neoplasm Invasiveness
• Up-Regulation