Epigenetic upregulation of Bak by ZBP-89 inhibits the growth of hepatocellular carcinoma.
Epigenetic upregulation of Bak by ZBP-89 inhibits the growth of hepatocellular carcinoma.
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DOI：
10.1016/j.bbamcr.2013.08.001
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发表时间：
2013-12
影响因子：
5.1
通讯作者：
Lai, Paul B. S.
中科院分区：
文献类型：
--
作者：
Ye, Cai Guo;Chen, George G.;Ho, Rocky L. K.;Merchant, Juanita L.;He, Ming-Liang;Lai, Paul B. S.
ZBP-89调节巴克以促进癌细胞的凋亡。本研究检测了ZBP-89是否通过肝细胞癌（HCC）的表观遗传机制调节巴克。我们首先证明了与相应的非癌组织相比，在HCC癌组织中巴克的表达降低，但DNMT 1和HDAC 3的水平增加。肝癌组织中巴克蛋白表达与DNMT 1水平呈负相关。给予ZBP-89下调HDAC 3表达并抑制HDAC和DNMT的活性，这导致维持组蛋白乙酰化状态，抑制甲基CpG结合蛋白2与基因组DNA的结合以及HCC细胞中巴克启动子中的去甲基化CpG岛。使用异种移植小鼠肿瘤模型，我们证明了ZBP-89或任一表观遗传酶的抑制剂可以刺激巴克表达，诱导细胞凋亡，并阻止肿瘤生长，并且当ZBP-89和酶抑制剂组合使用时达到最大效果。总之，ZBP-89通过靶向HCC中表观遗传途径的多个组分上调巴克的表达。
ZBP-89 regulates Bak to facilitate apoptosis in cancer cells. This study examined if ZBP-89 regulates Bak through an epigenetic mechanism in hepatocellular carcinoma (HCC). We first demonstrated that the expression of Bak was reduced but the levels of DNMT1 and HDAC3 were increased in HCC cancer tissues compared to the corresponding non-cancer tissues. Moreover, there was a negative correlation between Bak expression and DNMT1 levels in HCC. Administration of ZBP-89 downregulated HDAC3 expression and suppressed the activities of HDAC and DNMT, which led to maintenance of histone acetylation status, inhibited the binding of methyl-CpG-binding protein 2 to genomic DNA and demethylated CpG islands in the Bak promoter in HCC cells. Using the xenograft mouse tumor model, we demonstrated that ZBP-89 or inhibitors of either epigenetic enzymes could stimulate Bak expression, induce apoptosis, and arrest tumor growth and that the maximal effort was achieved when ZBP-89 and the enzyme inhibitors was used in combination. Conclusively, ZBP-89 upregulates the expression of Bak by targeting multiple components of the epigenetic pathway in HCC.
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影响因子：
4
作者：
Hu, RG;Zhai, QW;Liu, XY
通讯作者：
Liu, XY
影响因子：
6.4
作者：
Miao, Ji;Chen, George G.;Lai, Paul B. S.
通讯作者：
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
Baylin, SB
影响因子：
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作者：
Lee, Tong Ihn;Johnstone, Sarah E.;Young, Richard A.
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