Disruption of the EZH2/miRNA/β-catenin signaling suppresses aerobic glycolysis in glioma
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Yingyi Wang1,*, Min Wang2,*, Wenjin Wei1,*, Dongfeng Han1,*, Xincheng Chen1, Qi Hu1, Tianfu Yu1, Ning Liu1, Yongping You1, Junxia Zhang1
1Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
2Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
*These authors contributed equally to this work
Junxia Zhang, email: [email protected]
Keywords: EZH2, miRNA, β-catenin, aerobic glycolysis, glioma
Received: February 01, 2016 Accepted: June 12, 2016 Published: July 01, 2016
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.
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