Disruption of the EZH2/miRNA/β-catenin signaling suppresses aerobic glycolysis in glioma.

EZH2 is up-regulated in various cancer types, implicating its role in tumorigenesis. Our recent data have shown that repression of EZH2 inhibited glioma growth by inhibition β-catenin signaling. Here, we identified several miRNAs that were repressed by EZH2, which in turn regulate β-catenin expression by its 3'UTR, such as miR-1224-3p, miR-328 and miR-214. Further, EZH2 silenced miR-328 expression by binding to miR-328 promoter and promoting methylation of miR-328 promoter. Finally, miR-328 largely abrogated EZH2 effects on β-catenin expression and glucose metabolism in glioma cells. Taken together, we propose a model for a coordinated EZH2-β-catenin oncoprotein axis, and epigenetic link between histone modification and DNA methylation, mediated by EZH2-scilenced miRNAs.