Epigenetic activation of E-cadherin is a candidate therapeutic target in human hepatocellular carcinoma
Epigenetic activation of E-cadherin is a candidate therapeutic target in human hepatocellular carcinoma
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E-钙粘蛋白的表观遗传激活是人类肝细胞癌的候选治疗靶点
DOI：
10.3892/etm_00000082
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发表时间：
2010-05-01
影响因子：
2.7
通讯作者：
Fan, Hong
中科院分区：
文献类型：
--
作者：
Qiu, Xuemei;Qiao, Fengchang;Fan, Hong
E-钙粘蛋白是参与肿瘤抑制的关键细胞粘附分子，其在肝细胞癌（HCC）中经常改变，特别是在B型肝炎病毒相关肿瘤中。在这里，我们报告了表观遗传药物5-氮杂胞苷和阿司他丁A上调肝癌细胞中E-钙粘蛋白的表达。DNMT 1的缺失通过去甲基化恢复了E-钙粘蛋白的表达，而DNMT 3A或DNMT 3B的缺失则没有。活化的E-钙粘蛋白抑制HCC细胞集落形成。然而，E-钙粘蛋白的表达被HBx转染由于DNA甲基化诱导的肝癌细胞系中的DNMT 1的升高而被抑制。目前的研究表明，E-钙粘蛋白的表达在肝癌细胞中的表观遗传因子的调节，这表明了一个模式，恢复E-钙粘蛋白通过靶向其表观遗传机制。
E-cadherin is a key cell adhesion molecule implicated in tumor suppression that is frequently altered in hepatocellular carcinoma (HCC), particularly in hepatitis B virus-related tumors. Here, we report that the epigenetic drugs 5-azacytidine and trichostatin A up-regulated E-cadherin expression in HCC cells. The depletion of DNMT1 restored E-cadherin expression via demethylation, whereas the depletion of DNMT3A or DNMT3B did not. Activated E-cadherin suppressed HCC cell colony formation. However, E-cadherin expression was repressed by HBx transfection due to the DNA methylation induced by the elevation of DNMT1 in the HCC cell lines. The present study indicates that E-cadherin expression is regulated by epigenetic agents in HCC cells, which suggests a schema for restoring E-cadherin by targeting its epigenetic mechanism.