Histone deacetylase 1 is required for transforming growth factor-β1-induced epithelial-mesenchymal transition

Weiwei Lei, Kehua Zhang, Xinchao Pan, Ying Hu, Dongmei Wang, Xinwang Yuan, Guangwen Shu, Jianguo Song

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

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-β1 (TGF-β1)-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-β1-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-β1-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-β1-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-β1-induced EMT.

Original languageEnglish (US)
Pages (from-to)1489-1497
Number of pages9
JournalInternational Journal of Biochemistry and Cell Biology
Volume42
Issue number9
DOIs
StatePublished - Sep 1 2010

Keywords

  • E-cadherin
  • EMT
  • HDAC
  • Hepatocytes
  • TGF-β
  • ZO-1

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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