MiR-421 inhibits the malignant phenotype in glioma by directly targeting MEF2D.

MicroRNA-421 (miRNA-421) dysregulation has been found in various human tumors, however, the biological function and molecular mechanism of miR-421 in glioma remain unclear. In this study, we investigated the potential biological roles of miR-421 in glioma cell lines. First, we demonstrated that compared with that of low grade gliomas (LGG), miR-421 expression is much lower in high grade gliomas (HGG) within the CGGA (Chinese Glioma Genome Atlas) database. MiR-421 expression in 5 normal brain tissues and 20 glioma tissues were in agreement with the result in the CGGA. Second, exogenous expression of miR-421 inhibited glucose metabolism, invasion, angiogenesis and enhanced the radiosensitivity in glioma cell lines. Third, through an online database, myocyte enhancer factor 2D (MEF2D) was identified as a target of miR-421. Interestingly, down-regulation of MEF2D led to an inhibitory effect on glioma glucose metabolism, invasion, angiogenesis and enhancing effect on radiosensitivity, which was similar to the effects of the up-regulation of miR-421. Simultaneously, overexpression of MEF2D partially restored the effect of miR-421 on the glioma cell lines. Finally, in a xenograft model, overexpression of miR-421 suppressed tumorigenicity. These data collectively suggested miR-421 may suppress tumor-associated activity in gliomas by targeting MEF2D.