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

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.

Research highlights
► miR-218 is markedly downregulated in glioma cell lines and in primary glioma tissues.
► Upregulation of miR-218 dramatically reduces the invasive ability of glioma cells.
► Ectopic expression of miR-218 inactivates IKK-β/NF-κB signaling pathway.
► miR-218 directly targets the 3′-untranslated region (3′-UTR) of IKK-β.