Mutual regulation between CHD5 and EZH2 in hepatocellular carcinoma.
Mutual regulation between CHD5 and EZH2 in hepatocellular carcinoma.
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CHD5与EZH2在肝细胞癌中的相互调控
DOI：
10.18632/oncotarget.5724
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发表时间：
2015-12-01
期刊：
影响因子：
--
通讯作者：
Yin ZY
中科院分区：
文献类型：
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作者：
Xie CR;Li Z;Sun HG;Wang FQ;Sun Y;Zhao WX;Zhang S;Zhao WX;Wang XM;Yin ZY
染色体结构域解旋酶DNA结合蛋白5（CHD5）在许多癌症中充当肿瘤抑制因子。在本研究中，我们证明了肝细胞癌（HCC）组织中CHD5水平的降低与转移和预后不良显著相关。功能获得试验表明，CHD5抑制HCC细胞的运动和侵袭。随后的研究表明，在HCC细胞中，多梳阻遏复合物2（PRC2）介导的组蛋白H3在赖氨酸27（H3K27me3）处的三甲基化使CHD5表观遗传学沉默。此外，CHD5的过表达抑制了zeste同源物2（EZH2）的增强子并激活了PRC2靶基因，如p16和p21。染色质免疫沉淀和荧光素酶报告基因分析也表明，CHD5和EZH2相互结合的启动子和抑制转录。这些发现首次揭示了CHD5和EZH2之间的相互抑制调节，这可能为其对HCC的潜在治疗意义提供新的见解。
Chromodomain helicase DNA binding protein 5 (CHD5) acts as a tumor suppressor in many cancers. In the present study, we demonstrated that reduced levels of CHD5 in hepatocellular carcinoma (HCC) tissues were significantly associated with metastasis and poor prognosis. Gain-of-function assays revealed that CHD5 suppressed motility and invasion of HCC cells. Subsequent investigations showed that CHD5 was epigenetically silenced by polycomb repressive complex 2 (PRC2)-mediated the trimethylation of histone H3 at lysine 27 (H3K27me3) in HCC cells. Furthermore, overexpression of CHD5 repressed enhancer of zeste homolog 2 (EZH2) and activated PRC2 target genes, such as p16 and p21. Chromatin immunoprecipitation and luciferase reporter assays also showed that CHD5 and EZH2 bind to each other's promoters and inhibit transcription. These findings uncovered, for the first time, a mutual suppression regulation between CHD5 and EZH2, which may provide new insights into their potential therapeutic significance for HCC.