MiR-424 functions as a tumor suppressor in glioma cells and is down-regulated by DNA methylation

Glioma is one of the most lethal malignancies, and increasing reports revealed that microRNAs (miRNAs), a class of small non-coding RNAs, play a critical role in the development and pathology of human gliomas. MiR-424 has been found to be dysregulated in many different types of human cancers. However, the clinical significance and function of miR-424 in glioma remains unclear. Here, based on RTq-PCR analysis in 148 clinical specimens, we found miR-424 expression was significantly decreased in glioma tumor tissues than in adjacent non-neoplastic brain tissues, and decreased miR-424 expression was associated with glioma KPS (P = 0.009) and high grades (P = 0.029). In vitro cellular function assays further revealed that miR-424 inhibited cell invasion and migration, and promoted cell apoptosis. In addition, based on DNA methylation analysis on clinical specimens and cell lines, we found miR-424 promoter CpG island was frequently methylated and correlated with glioma high grades (P = 0.035) and IDH mutation status (P = 0.042). Moreover, the promoter CpG island was demethylated by 5-aza-2'-deoxycytidine treatment in a time-dependent manner and the expression levels of miR-424 were gradually induced and increased. Taken together, our data suggest that the promoter region CpG island methylation is associated with tumor suppressive miR-424 silencing and the pathology of human gliomas.