TET-Mediated Sequestration of miR-26 Drives EZH2 Expression and Gastric Carcinogenesis
TET-Mediated Sequestration of miR-26 Drives EZH2 Expression and Gastric Carcinogenesis
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TET 介导的 miR-26 隔离驱动 EZH2 表达和胃癌发生
DOI：
10.1158/0008-5472.can-16-2964
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发表时间：
2017-11-15
期刊：
影响因子：
11.2
通讯作者：
He, Zhimin
中科院分区：
文献类型：
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作者：
Deng, Min;Zhang, Ruixin;He, Zhimin
Tet家族的DNA去甲基酶在多种人类癌症中发挥肿瘤抑制作用，但它们在胃癌发生发展中的致病作用和作用机制尚不清楚。在这里，我们报告了Tet在胃癌中转录上调，它与不良预后相关。机制研究表明，Tet通过与miR-26相互作用的3‘非编码区功能促进了胃癌的发生。这种相互作用导致miR-26与其靶标EZH2隔离，从而释放对EZH2的抑制，从而导致EZH2在胃癌中过表达。我们的发现揭示了Tet家族蛋白在促进胃癌发生中的一种新的非编码功能。(C)2017年AACR。
DNA demethylases of the TET family function as tumor suppressors in various human cancers, but their pathogenic contributions and mechanisms of action in gastric carcinogenesis and progression remain unclear. Here, we report that TET is transcriptionally upregulated in gastric cancer, where it correlates with poor prognosis. Mechanistic investigations revealed that TET facilitated gastric carcinogenesis through a noncoding function of the 3'UTR, which interacted with miR-26. This interaction resulted in sequestration of miR-26 from its target EZH2, which released the suppression on EZH2, and thereby led to EZH2 overexpression in gastric cancer. Our findings uncover a novel noncoding function for TET family proteins in facilitating gastric carcinogenesis. (C) 2017 AACR.