Sustained JNK1 activation is associated with altered histone H3 methylations in human liver cancer

Qingshan Chang; Yadong Zhang; Kevin J. Beezhold; Deepak Bhatia; Hongwen Zhao; Jianguo Chen; Vince Castranova; Xianglin Shi; Fei Chen

doi:10.1016/j.jhep.2008.07.037

Sustained JNK1 activation is associated with altered histone H3 methylations in human liver cancer

Qingshan Chang, Yadong Zhang, Kevin J. Beezhold, Deepak Bhatia, Hongwen Zhao, Jianguo Chen, Vince Castranova, Xianglin Shi, Fei Chen

Toxicology and Cancer Biology

Research output: Contribution to journal › Article › peer-review

116 Scopus citations

Abstract

Background/Aims: Aberrant c-Jun N-terminal kinase (JNK) activation has been linked to hepatocellular carcinoma (HCC) in mouse models. It remains unclear whether JNK activation plays an important role in human HCC and, if so, how JNK signaling contributes to the initiation or progression of HCC. Methods: The JNK activation, global gene expression, and the status of histone H3 methylations were measured in 31 primary human hepatocellular carcinoma (HCC) samples paired with the adjacent non-cancerous (ANC) tissues. Results: Enhanced JNK1 activation was noted in 17 out of 31 HCC samples (55%) relative to the corresponding ANC tissues, whereas JNK2 activation was roughly equal between HCC and ANC tissues. This enhancement in JNK1 activation is associated with an increased tumor size and a lack of encapsulation of the tumors. In addition, an association of JNK1 activation with the histone H3 lysines 4 and 9 tri-methylation was observed in the HCC tissues, which leads to an elevated expression of genes regulating cell growth and a decreased expression of the genes for cell differentiation and the p450 family members in HCC. Conclusions: These results, thus, suggest that JNK1 plays important roles in the development of human HCC partially through the epigenetic mechanisms.

Original language	English
Pages (from-to)	323-333
Number of pages	11
Journal	Journal of Hepatology
Volume	50
Issue number	2
DOIs	https://doi.org/10.1016/j.jhep.2008.07.037
State	Published - Feb 2009

Bibliographical note

Funding Information:
Grant support: This research was supported by intramural research grant from the National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention of the USA to F. Chen (70036) and partially supported from F. Chen’s personal account. X. Shi was supported by NIH Grants 5R01CA119028 and 5R01CA116697. We are indebted to Dr. Hiroshi Nishina, Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, for his gift of wild-type and SEK1 −/− ES cells. We thank the members in the Pathology and Physiology Research Branch of NIOSH for suggestions and critical reading.

Keywords

EZH2
H3K4me3
HCC
JNK
Tumor suppressor

ASJC Scopus subject areas

Hepatology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jhep.2008.07.037

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@article{3c0c3cd4aecb405a97745facb19549e2,

title = "Sustained JNK1 activation is associated with altered histone H3 methylations in human liver cancer",

abstract = "Background/Aims: Aberrant c-Jun N-terminal kinase (JNK) activation has been linked to hepatocellular carcinoma (HCC) in mouse models. It remains unclear whether JNK activation plays an important role in human HCC and, if so, how JNK signaling contributes to the initiation or progression of HCC. Methods: The JNK activation, global gene expression, and the status of histone H3 methylations were measured in 31 primary human hepatocellular carcinoma (HCC) samples paired with the adjacent non-cancerous (ANC) tissues. Results: Enhanced JNK1 activation was noted in 17 out of 31 HCC samples (55%) relative to the corresponding ANC tissues, whereas JNK2 activation was roughly equal between HCC and ANC tissues. This enhancement in JNK1 activation is associated with an increased tumor size and a lack of encapsulation of the tumors. In addition, an association of JNK1 activation with the histone H3 lysines 4 and 9 tri-methylation was observed in the HCC tissues, which leads to an elevated expression of genes regulating cell growth and a decreased expression of the genes for cell differentiation and the p450 family members in HCC. Conclusions: These results, thus, suggest that JNK1 plays important roles in the development of human HCC partially through the epigenetic mechanisms.",

keywords = "EZH2, H3K4me3, HCC, JNK, Tumor suppressor",

author = "Qingshan Chang and Yadong Zhang and Beezhold, {Kevin J.} and Deepak Bhatia and Hongwen Zhao and Jianguo Chen and Vince Castranova and Xianglin Shi and Fei Chen",

note = "Funding Information: Grant support: This research was supported by intramural research grant from the National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention of the USA to F. Chen (70036) and partially supported from F. Chen{\textquoteright}s personal account. X. Shi was supported by NIH Grants 5R01CA119028 and 5R01CA116697. We are indebted to Dr. Hiroshi Nishina, Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, for his gift of wild-type and SEK1 −/− ES cells. We thank the members in the Pathology and Physiology Research Branch of NIOSH for suggestions and critical reading. ",

year = "2009",

month = feb,

doi = "10.1016/j.jhep.2008.07.037",

language = "English",

volume = "50",

pages = "323--333",

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T1 - Sustained JNK1 activation is associated with altered histone H3 methylations in human liver cancer

AU - Chang, Qingshan

AU - Zhang, Yadong

AU - Beezhold, Kevin J.

AU - Bhatia, Deepak

AU - Zhao, Hongwen

AU - Chen, Jianguo

AU - Castranova, Vince

AU - Shi, Xianglin

AU - Chen, Fei

N1 - Funding Information: Grant support: This research was supported by intramural research grant from the National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention of the USA to F. Chen (70036) and partially supported from F. Chen’s personal account. X. Shi was supported by NIH Grants 5R01CA119028 and 5R01CA116697. We are indebted to Dr. Hiroshi Nishina, Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, for his gift of wild-type and SEK1 −/− ES cells. We thank the members in the Pathology and Physiology Research Branch of NIOSH for suggestions and critical reading.

PY - 2009/2

Y1 - 2009/2

N2 - Background/Aims: Aberrant c-Jun N-terminal kinase (JNK) activation has been linked to hepatocellular carcinoma (HCC) in mouse models. It remains unclear whether JNK activation plays an important role in human HCC and, if so, how JNK signaling contributes to the initiation or progression of HCC. Methods: The JNK activation, global gene expression, and the status of histone H3 methylations were measured in 31 primary human hepatocellular carcinoma (HCC) samples paired with the adjacent non-cancerous (ANC) tissues. Results: Enhanced JNK1 activation was noted in 17 out of 31 HCC samples (55%) relative to the corresponding ANC tissues, whereas JNK2 activation was roughly equal between HCC and ANC tissues. This enhancement in JNK1 activation is associated with an increased tumor size and a lack of encapsulation of the tumors. In addition, an association of JNK1 activation with the histone H3 lysines 4 and 9 tri-methylation was observed in the HCC tissues, which leads to an elevated expression of genes regulating cell growth and a decreased expression of the genes for cell differentiation and the p450 family members in HCC. Conclusions: These results, thus, suggest that JNK1 plays important roles in the development of human HCC partially through the epigenetic mechanisms.

AB - Background/Aims: Aberrant c-Jun N-terminal kinase (JNK) activation has been linked to hepatocellular carcinoma (HCC) in mouse models. It remains unclear whether JNK activation plays an important role in human HCC and, if so, how JNK signaling contributes to the initiation or progression of HCC. Methods: The JNK activation, global gene expression, and the status of histone H3 methylations were measured in 31 primary human hepatocellular carcinoma (HCC) samples paired with the adjacent non-cancerous (ANC) tissues. Results: Enhanced JNK1 activation was noted in 17 out of 31 HCC samples (55%) relative to the corresponding ANC tissues, whereas JNK2 activation was roughly equal between HCC and ANC tissues. This enhancement in JNK1 activation is associated with an increased tumor size and a lack of encapsulation of the tumors. In addition, an association of JNK1 activation with the histone H3 lysines 4 and 9 tri-methylation was observed in the HCC tissues, which leads to an elevated expression of genes regulating cell growth and a decreased expression of the genes for cell differentiation and the p450 family members in HCC. Conclusions: These results, thus, suggest that JNK1 plays important roles in the development of human HCC partially through the epigenetic mechanisms.

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KW - Tumor suppressor

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JO - Journal of Hepatology

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Sustained JNK1 activation is associated with altered histone H3 methylations in human liver cancer

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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