Histone deacetylase 1 is required for transforming growth factor-β1-induced epithelial-mesenchymal transition
Histone deacetylase 1 is required for transforming growth factor-β1-induced epithelial-mesenchymal transition
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DOI：
10.1016/j.biocel.2010.05.006
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发表时间：
2010-09-01
影响因子：
4
通讯作者：
Song, Jianguo
中科院分区：
文献类型：
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作者：
Lei, Weiwei;Zhang, Kehua;Song, Jianguo
上皮间质转化（EMT）与胚胎发育、纤维化和肿瘤转移有关。组蛋白脱乙酰酶（HDAC）在控制各种生理和病理事件中也发挥着重要作用。然而，HDAC 是否参与肝细胞 EMT 的控制仍不清楚。三种结构上不相关的 HDAC 抑制剂完全抑制 AML-12 小鼠肝细胞和原代小鼠肝细胞中转化生长因子-β 1 (TGF-β 1) 诱导的 EMT。 HDAC1 显性失活突变体的表达（但不是 HDAC2）或 RNAi 下调 HDAC1 但不是 HDAC2 抑制了 TGF-β 1 诱导的 EMT。此外，HDAC 抑制剂 TSA 和 HDAC1 RNAi 均可阻断细胞迁移。在侵袭性肝细胞癌 (HCC) 样本中检测到 HDAC1 过度表达。进一步研究表明，TGF-β1诱导的EMT过程中ZO-1和E-cadherin的mRNA水平下调，并且HDAC1可以下调ZO-1和E-cadherin的启动子活性。结论：我们的结果表明 HDAC1 是 TGF-β 1 诱导的 EMT 和肝细胞细胞迁移所必需的。 HDAC1 在大多数侵袭性 HCC 样本中的高表达水平表明，HDAC1 通过促进 EMT 可能与 HCC 的侵袭性相关。数据还表明，HDAC1 对 ZO-1 和 E-cadherin 转录的抑制可能参与了 TGF-β1 诱导的 EMT。 (C) 2010 Elsevier Ltd. 保留所有权利。
Epithelial-mesenchymal transition (EMT) has been implicated in embryonic development, fibrosis, and tumor metastasis. Histone deacetylases ( HDACs) also play important roles in the control of various physiological and pathological events. However, whether HDACs are involved in the control of EMT in liver cells remains unidentified. Three structurally unrelated HDAC inhibitors completely suppress transforming growth factor-beta 1 (TGF-beta 1)-induced EMT in AML-12 murine hepatocytes and primary mouse hepatocytes. Expression of a dominant-negative mutant of HDAC1 but not HDAC2 or downregulation of HDAC1 but not HDAC2 by RNAi suppressed TGF-beta 1-induced EMT. In addition, both HDAC inhibitor TSA and HDAC1 RNAi blocked cell migration. Overexpression of HDAC1 in invasive hepatocellular carcinoma (HCC) samples was detected. Further study showed that the mRNA levels of ZO-1 and E-cadherin were downregulated during TGF-beta 1 -induced EMT, and HDAC1 can downregulate the promoter activities of ZO-1 and E-cadherin. Conclusions: our results demonstrate that HDAC1 is required for TGF-beta 1-induced EMT and cell migration in hepatocytes. Its high expression levels in majority of invasive HCC samples suggest that, by promoting EMT, HDAC1 can be related with the invasiveness of HCC. The data also suggest that the repression of transcription of ZO-1 and E-cadherin by HDAC1 may be involved in TGF-beta 1-induced EMT. (C) 2010 Elsevier Ltd. All rights reserved.