title: STAT3 repressed USP7 expression is crucial for colon cancer development.
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.
authors: Department of General Surgery, Central Hospital of Fengxian District, Shanghai, China.
authors: Zhi
authors: Z
authors: Yang
authors: Shoujun
authors: S
authors: Huo
authors: Yuanzhou
authors: Y
authors: Shan
authors: Haijun
authors: H
authors: Liu
authors: Yume
authors: Y
authors: Xu
authors: Kai
authors: K
authors: Yao
authors: Xianwei
authors: X
authors: Li
authors: Xueli
authors: X
authors: Zhang
mesh_terms: D001665:Binding Sites / Q000235:genetics; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000209:etiology* / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D045325:HCT116 Cells; D057809:HEK293 Cells; D056284:Histone Deacetylase 1 / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D053858:Metabolic Networks and Pathways; D011401:Promoter Regions, Genetic; D055550:Protein Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000076084:Ubiquitin-Specific Peptidase 7
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C464569:USP7 protein, human; D043222:Ubiquitin Thiolesterase; D000076084:Ubiquitin-Specific Peptidase 7; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1