Negative modulation of the epigenetic regulator, UHRF1, by thyroid hormone receptors suppresses liver cancer cell growth

Sheng Ming Wu, Wan Li Cheng, Chia Jung Liao, Hsiang Cheng Chi, Yang Hsiang Lin, Yi Hsin Tseng, Chung Ying Tsai, Ching Ying Chen, Syuan Ling Lin, Wei Jan Chen, Yung Hsin Yeh, Chi Ying F Huang, Ming Huang Chen, Yi Chen Yeh, Kwang Huei Lin

研究成果: 雜誌貢獻文章

16 引文 (Scopus)

摘要

The thyroid hormone, 3,3,5-triiodo-l-thyronine (T3), mediates several physiological processes, including embryonic development, cellular differentiation, metabolism and regulation of cell proliferation. Thyroid hormone (T3) and its receptor (TR) are involved in metabolism and growth. In addition to their developmental and metabolic functions, TRs play a tumor suppressor role, and therefore, their aberrant expression can lead to tumor transformation. Aberrant epigenetic silencing of tumor suppressor genes promotes cancer progression. The epigenetic regulator, Ubiquitin-like with PHD and ring finger domains 1 (UHRF1), is overexpressed in various cancers. In our study, we demonstrated that T3 negatively regulates UHRF1 expression, both in vitro and in vivo. Our results further indicate that UHRF1 regulation by T3 is indirect and mediated by Sp1. Sp1-binding elements of UHRF1 were identified at positions -664/-505 of the promoter region using the luciferase and chromatin immunoprecipitation assays. Notably, UHRF1 and Sp1 levels were elevated in subgroups of hepatocellular carcinoma patients and inversely correlated with TRα1 expression. Knockdown of UHRF1 expression should therefore provide a means to inhibit hepatoma cell proliferation. Expression of UHRF1 was downregulated by TRs, in turn, relieving silencing of the UHRF1 target gene, p21. Based on the collective findings, we propose that T3/TR signaling induces hepatoma cell growth inhibition via UHRF1 repression.
原文英語
頁(從 - 到)37-49
頁數13
期刊International Journal of Cancer
137
發行號1
DOIs
出版狀態已發佈 - 七月 1 2015
對外發佈Yes

指紋

Thyroid Hormone Receptors
Liver Neoplasms
Epigenomics
Hepatocellular Carcinoma
Growth
Thyroid Hormones
Neoplasms
Cell Proliferation
Thyronines
Physiological Phenomena
Chromatin Immunoprecipitation
Ubiquitin
Tumor Suppressor Genes
Luciferases
Genetic Promoter Regions
Fingers
Embryonic Development
Down-Regulation
Genes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

引用此文

Negative modulation of the epigenetic regulator, UHRF1, by thyroid hormone receptors suppresses liver cancer cell growth. / Wu, Sheng Ming; Cheng, Wan Li; Liao, Chia Jung; Chi, Hsiang Cheng; Lin, Yang Hsiang; Tseng, Yi Hsin; Tsai, Chung Ying; Chen, Ching Ying; Lin, Syuan Ling; Chen, Wei Jan; Yeh, Yung Hsin; Huang, Chi Ying F; Chen, Ming Huang; Yeh, Yi Chen; Lin, Kwang Huei.

於: International Journal of Cancer, 卷 137, 編號 1, 01.07.2015, p. 37-49.

研究成果: 雜誌貢獻文章

Wu, SM, Cheng, WL, Liao, CJ, Chi, HC, Lin, YH, Tseng, YH, Tsai, CY, Chen, CY, Lin, SL, Chen, WJ, Yeh, YH, Huang, CYF, Chen, MH, Yeh, YC & Lin, KH 2015, 'Negative modulation of the epigenetic regulator, UHRF1, by thyroid hormone receptors suppresses liver cancer cell growth', International Journal of Cancer, 卷 137, 編號 1, 頁 37-49. https://doi.org/10.1002/ijc.29368
Wu, Sheng Ming ; Cheng, Wan Li ; Liao, Chia Jung ; Chi, Hsiang Cheng ; Lin, Yang Hsiang ; Tseng, Yi Hsin ; Tsai, Chung Ying ; Chen, Ching Ying ; Lin, Syuan Ling ; Chen, Wei Jan ; Yeh, Yung Hsin ; Huang, Chi Ying F ; Chen, Ming Huang ; Yeh, Yi Chen ; Lin, Kwang Huei. / Negative modulation of the epigenetic regulator, UHRF1, by thyroid hormone receptors suppresses liver cancer cell growth. 於: International Journal of Cancer. 2015 ; 卷 137, 編號 1. 頁 37-49.
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abstract = "The thyroid hormone, 3,3,5-triiodo-l-thyronine (T3), mediates several physiological processes, including embryonic development, cellular differentiation, metabolism and regulation of cell proliferation. Thyroid hormone (T3) and its receptor (TR) are involved in metabolism and growth. In addition to their developmental and metabolic functions, TRs play a tumor suppressor role, and therefore, their aberrant expression can lead to tumor transformation. Aberrant epigenetic silencing of tumor suppressor genes promotes cancer progression. The epigenetic regulator, Ubiquitin-like with PHD and ring finger domains 1 (UHRF1), is overexpressed in various cancers. In our study, we demonstrated that T3 negatively regulates UHRF1 expression, both in vitro and in vivo. Our results further indicate that UHRF1 regulation by T3 is indirect and mediated by Sp1. Sp1-binding elements of UHRF1 were identified at positions -664/-505 of the promoter region using the luciferase and chromatin immunoprecipitation assays. Notably, UHRF1 and Sp1 levels were elevated in subgroups of hepatocellular carcinoma patients and inversely correlated with TRα1 expression. Knockdown of UHRF1 expression should therefore provide a means to inhibit hepatoma cell proliferation. Expression of UHRF1 was downregulated by TRs, in turn, relieving silencing of the UHRF1 target gene, p21. Based on the collective findings, we propose that T3/TR signaling induces hepatoma cell growth inhibition via UHRF1 repression.",
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AU - Cheng, Wan Li

AU - Liao, Chia Jung

AU - Chi, Hsiang Cheng

AU - Lin, Yang Hsiang

AU - Tseng, Yi Hsin

AU - Tsai, Chung Ying

AU - Chen, Ching Ying

AU - Lin, Syuan Ling

AU - Chen, Wei Jan

AU - Yeh, Yung Hsin

AU - Huang, Chi Ying F

AU - Chen, Ming Huang

AU - Yeh, Yi Chen

AU - Lin, Kwang Huei

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N2 - The thyroid hormone, 3,3,5-triiodo-l-thyronine (T3), mediates several physiological processes, including embryonic development, cellular differentiation, metabolism and regulation of cell proliferation. Thyroid hormone (T3) and its receptor (TR) are involved in metabolism and growth. In addition to their developmental and metabolic functions, TRs play a tumor suppressor role, and therefore, their aberrant expression can lead to tumor transformation. Aberrant epigenetic silencing of tumor suppressor genes promotes cancer progression. The epigenetic regulator, Ubiquitin-like with PHD and ring finger domains 1 (UHRF1), is overexpressed in various cancers. In our study, we demonstrated that T3 negatively regulates UHRF1 expression, both in vitro and in vivo. Our results further indicate that UHRF1 regulation by T3 is indirect and mediated by Sp1. Sp1-binding elements of UHRF1 were identified at positions -664/-505 of the promoter region using the luciferase and chromatin immunoprecipitation assays. Notably, UHRF1 and Sp1 levels were elevated in subgroups of hepatocellular carcinoma patients and inversely correlated with TRα1 expression. Knockdown of UHRF1 expression should therefore provide a means to inhibit hepatoma cell proliferation. Expression of UHRF1 was downregulated by TRs, in turn, relieving silencing of the UHRF1 target gene, p21. Based on the collective findings, we propose that T3/TR signaling induces hepatoma cell growth inhibition via UHRF1 repression.

AB - The thyroid hormone, 3,3,5-triiodo-l-thyronine (T3), mediates several physiological processes, including embryonic development, cellular differentiation, metabolism and regulation of cell proliferation. Thyroid hormone (T3) and its receptor (TR) are involved in metabolism and growth. In addition to their developmental and metabolic functions, TRs play a tumor suppressor role, and therefore, their aberrant expression can lead to tumor transformation. Aberrant epigenetic silencing of tumor suppressor genes promotes cancer progression. The epigenetic regulator, Ubiquitin-like with PHD and ring finger domains 1 (UHRF1), is overexpressed in various cancers. In our study, we demonstrated that T3 negatively regulates UHRF1 expression, both in vitro and in vivo. Our results further indicate that UHRF1 regulation by T3 is indirect and mediated by Sp1. Sp1-binding elements of UHRF1 were identified at positions -664/-505 of the promoter region using the luciferase and chromatin immunoprecipitation assays. Notably, UHRF1 and Sp1 levels were elevated in subgroups of hepatocellular carcinoma patients and inversely correlated with TRα1 expression. Knockdown of UHRF1 expression should therefore provide a means to inhibit hepatoma cell proliferation. Expression of UHRF1 was downregulated by TRs, in turn, relieving silencing of the UHRF1 target gene, p21. Based on the collective findings, we propose that T3/TR signaling induces hepatoma cell growth inhibition via UHRF1 repression.

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