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

doi:10.1016/j.biocel.2010.05.006

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

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67 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 language	English (US)
Pages (from-to)	1489-1497
Number of pages	9
Journal	International Journal of Biochemistry and Cell Biology
Volume	42
Issue number	9
DOIs	https://doi.org/10.1016/j.biocel.2010.05.006
State	Published - Sep 2010

Keywords

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

ASJC Scopus subject areas

Biochemistry
Cell Biology

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10.1016/j.biocel.2010.05.006

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@article{5cd80fd33e094cd59247d4ef344f3296,

title = "Histone deacetylase 1 is required for transforming growth factor-β1-induced epithelial-mesenchymal transition",

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.",

keywords = "E-cadherin, EMT, HDAC, Hepatocytes, TGF-β, ZO-1",

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

note = "Funding Information: We are grateful to Dr. Tony Kouzarides for the plasmids for wild type HDAC1 and 2, Dr. Amparo Cano for the plasmid of E-cadherin promoter (position −178 to +92) in pGL2. We also thank members of the laboratory for many helpful discussions. This work was supported by The Natural Science Foundation of China [grant numbers 30730023 , 30721065 , 30623003 ]; the National Basic Research Program of China [grant number 2007CB947900 ]; and the Shanghai Science Committee [grant number 06DZ22032 , 088014199 ].",

year = "2010",

month = sep,

doi = "10.1016/j.biocel.2010.05.006",

language = "English (US)",

volume = "42",

pages = "1489--1497",

journal = "International Journal of Biochemistry",

issn = "1357-2725",

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TY - JOUR

T1 - Histone deacetylase 1 is required for transforming growth factor-β1-induced epithelial-mesenchymal transition

AU - Lei, Weiwei

AU - Zhang, Kehua

AU - Pan, Xinchao

AU - Hu, Ying

AU - Wang, Dongmei

AU - Yuan, Xinwang

AU - Shu, Guangwen

AU - Song, Jianguo

N1 - Funding Information: We are grateful to Dr. Tony Kouzarides for the plasmids for wild type HDAC1 and 2, Dr. Amparo Cano for the plasmid of E-cadherin promoter (position −178 to +92) in pGL2. We also thank members of the laboratory for many helpful discussions. This work was supported by The Natural Science Foundation of China [grant numbers 30730023 , 30721065 , 30623003 ]; the National Basic Research Program of China [grant number 2007CB947900 ]; and the Shanghai Science Committee [grant number 06DZ22032 , 088014199 ].

PY - 2010/9

Y1 - 2010/9

N2 - 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.

AB - 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.

KW - E-cadherin

KW - EMT

KW - HDAC

KW - Hepatocytes

KW - TGF-β

KW - ZO-1

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U2 - 10.1016/j.biocel.2010.05.006

DO - 10.1016/j.biocel.2010.05.006

M3 - Article

C2 - 20580679

AN - SCOPUS:77955094541

SN - 1357-2725

VL - 42

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EP - 1497

JO - International Journal of Biochemistry

JF - International Journal of Biochemistry

IS - 9

ER -

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

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