TET 介导的 miR-26 隔离驱动 EZH2 表达和胃癌发生。
TET-Mediated Sequestration of miR-26 Drives EZH2 Expression and Gastric Carcinogenesis.
机构信息
Cancer Hospital and Cancer Research Institute, Guangzhou Medical University, Guangzhou, Guangdong, China.
Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
出版信息
Cancer Res. 2017 Nov 15;77(22):6069-6082. doi: 10.1158/0008-5472.CAN-16-2964. Epub 2017 Sep 18.
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. .
TET 家族的 DNA 去甲基化酶在多种人类癌症中作为肿瘤抑制因子发挥作用，但它们在胃癌发生和发展中的致病贡献和作用机制仍不清楚。在这里，我们报告 TET 在胃癌中转录上调，与预后不良相关。机制研究表明，TET 通过 3'UTR 的非编码功能促进胃癌发生，该功能与 miR-26 相互作用。这种相互作用导致 miR-26 与其靶基因 EZH2 分离，从而解除了对 EZH2 的抑制作用，导致胃癌中 EZH2 过表达。我们的研究结果揭示了 TET 家族蛋白在促进胃癌发生中的一种新的非编码功能。
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