E-钙黏蛋白的表观遗传激活是人类肝细胞癌的一个候选治疗靶点。
Epigenetic activation of E-cadherin is a candidate therapeutic target in human hepatocellular carcinoma.
作者信息
Qiu Xuemei, Qiao Fengchang, Su Xianwei, Zhao Zhujiang, Fan Hong
机构信息
Key Laboratory of Developmental Genes and Human Diseases, Ministry of Education;
出版信息
Exp Ther Med. 2010 May;1(3):519-523. doi: 10.3892/etm_00000082. Epub 2010 May 1.
Abstract
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.
摘要
E-钙黏蛋白是一种与肿瘤抑制相关的关键细胞黏附分子，在肝细胞癌（HCC）中经常发生改变，尤其是在乙型肝炎病毒相关肿瘤中。在此，我们报告表观遗传药物5-氮杂胞苷和曲古抑菌素A上调了肝癌细胞中E-钙黏蛋白的表达。DNMT1的缺失通过去甲基化恢复了E-钙黏蛋白的表达，而DNMT3A或DNMT3B的缺失则没有。激活的E-钙黏蛋白抑制了肝癌细胞集落的形成。然而，由于肝癌细胞系中DNMT1升高诱导的DNA甲基化，HBx转染会抑制E-钙黏蛋白的表达。本研究表明，E-钙黏蛋白的表达受肝癌细胞中表观遗传药物的调节，这提示了一种通过靶向其表观遗传机制来恢复E-钙黏蛋白的方案。
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