STAT3 repressed USP7 expression is crucial for colon cancer development

Zhi Yang; Shoujun Huo; Yuanzhou Shan; Haijun Liu; Yume Xu; Kai Yao; Xianwei Li; Xueli Zhang

doi:10.1016/j.febslet.2012.06.025

STAT3 repressed USP7 expression is crucial for colon cancer development

FEBS Lett. 2012 Sep 21;586(19):3013-7. doi: 10.1016/j.febslet.2012.06.025. Epub 2012 Jun 27.

Authors

Zhi Yang¹, Shoujun Huo, Yuanzhou Shan, Haijun Liu, Yume Xu, Kai Yao, Xianwei Li, Xueli Zhang

Affiliation

¹ Department of General Surgery, Central Hospital of Fengxian District, Shanghai, China.

PMID: 22750444
DOI: 10.1016/j.febslet.2012.06.025

Abstract

Interleukin-6 (IL-6) induced STAT3 activation is viewed as crucial for multiple tumor growth and metastasis, including colon cancer. However, the molecular mechanisms remain largely unexplored. Here, we show that expression of ubiquitin-specific protease 7 (USP7), a deubiquitylating enzyme, is decreased in STAT3-positive tumors. IL-6 administration or transfection of a constitutively activated STAT3 in SW480 cells also repressed USP mRNA expression. Using luciferase reporter and ChIP assay, we found that STAT3 bound to the promoter region of USP7 and inhibited its activity through recruiting HDAC1. As a result of the decline of USP7 expression, endogenous P53 protein level was decreased. Thus, our results suggest a previously unknown STAT3-USP7-P53 molecular network controlling colon cancer development.

MeSH terms

Binding Sites / genetics
Cell Line, Tumor
Colonic Neoplasms / etiology*
Colonic Neoplasms / genetics
Colonic Neoplasms / metabolism*
Down-Regulation / drug effects
HCT116 Cells
HEK293 Cells
Histone Deacetylase 1 / metabolism
Humans
Interleukin-6 / pharmacology
Metabolic Networks and Pathways
Promoter Regions, Genetic
Protein Stability
RNA, Messenger / genetics
RNA, Messenger / metabolism
RNA, Neoplasm / genetics
RNA, Neoplasm / metabolism
STAT3 Transcription Factor / genetics
STAT3 Transcription Factor / metabolism*
Signal Transduction
Transfection
Tumor Suppressor Protein p53 / metabolism
Ubiquitin Thiolesterase / antagonists & inhibitors
Ubiquitin Thiolesterase / genetics
Ubiquitin Thiolesterase / metabolism*
Ubiquitin-Specific Peptidase 7

Substances

IL6 protein, human
Interleukin-6
RNA, Messenger
RNA, Neoplasm
STAT3 Transcription Factor
STAT3 protein, human
TP53 protein, human
Tumor Suppressor Protein p53
USP7 protein, human
Ubiquitin Thiolesterase
Ubiquitin-Specific Peptidase 7
HDAC1 protein, human
Histone Deacetylase 1