MicroRNA-204, a direct negative regulator of ezrin gene expression, inhibits glioma cell migration and invasion.

Abstract

Ezrin is overexpressed in a variety of neoplastic cells and involved in the later stages of tumor progression and metastasis. Ezrin expression can be regulated at both the transcriptional and post-transcriptional levels. We used a combination of bioinformatics and experimental techniques to demonstrate that the miR-204 is a direct negative regulator of ezrin. Overexpression of miR-204 mimics decreased the activity of a luciferase reporter containing the ezrin 3' UTR and led to repression of ezrin protein. In contrast, ectopic expression of miR-204 inhibitor elevated ezrin expression. We also show that miR-204 is down-regulated in a panel of glioma tissues and in high invasive glioma cell lines we examined. Moreover, miR-204 mimics significantly reduced glioma cell migration and invasion, while miR-204 inhibitor generated the opposite results. Finally, overexpression of miR-204 and knockdown of ezrin reduced glioma cell invasion, and these effects could be rescued by re-expression of ezrin. These findings reveal that miR-204 could be partly due to its inhibitory effects on glioma cell migration and invasion through regulating ezrin expression.