Disruption of the EZH2/miRNA/β-catenin signaling suppresses aerobic glycolysis in glioma.
Disruption of the EZH2/miRNA/β-catenin signaling suppresses aerobic glycolysis in glioma.
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EZH2/miRNA/β-连环蛋白信号传导的破坏可抑制神经胶质瘤中的有氧糖酵解
DOI：
10.18632/oncotarget.10370
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发表时间：
2016-08-02
期刊：
影响因子：
--
通讯作者：
Zhang J
中科院分区：
文献类型：
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作者：
Wang Y;Wang M;Wei W;Han D;Chen X;Hu Q;Yu T;Liu N;You Y;Zhang J
EZH2在各种癌症类型中表达上调，暗示其在肿瘤发生中的作用。我们最近的数据表明，抑制EZH2型通过抑制β-连环蛋白信号来抑制胶质瘤的生长。在这里，我们发现了几个受EZH2抑制的miRNA，这些miRNA通过其3‘端非编码区调控β-catenin的表达，如miR-1224-3p、miR-328和miR-214。此外，EZH2通过与miR-328启动子结合并促进miR-328启动子甲基化来抑制miR-328的表达。最后，miR328在很大程度上消除了EZH2对胶质瘤细胞β-连环蛋白表达和葡萄糖代谢的影响。综上所述，我们提出了一个协调的EZH2-β-连环素癌蛋白轴的模型，以及组蛋白修饰和DNA甲基化之间的表观遗传学联系，由EZH2型干扰的miRNA介导。
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.