title: Aberrant Expression of CUL4A Is Associated with IL-6/ STAT3 Activation in Colorectal Cancer Progression.
abstract: Although it has been indicated that the cytokine interleukin-6 (IL-6) promotes colorectal cancer (CRC) tumorigenesis in tumor microenvironment, the mechanisms related to IL-6-induced tumor progression are still not well understood.
  
  
  
  First, the correlation between pSTAT3, CUL4A and ZEB1 was analyzed using immunocytochemistry. Logistic regression analysis was then used to observe the relationship between levels of pSTAT3, CUL4A and ZEB1 and clinicopathological characteristics. Finally, the mechanism of the effect of the expression level of pSTAT3, CUL4A and ZEB1 on cell invasion ability was verified by cell experiment.
  
  
  
  We discovered that the increased expression levels of pSTAT3, CUL4A and ZEB1 had significant relationships in CRC patients. These up-regulated expression levels were also closely associated with CRC aggressiveness. Furthermore, in vitro, we discovered that expression levels of CUL4A and ZEB1 were significantly up-regulated when IL-6 stimulated. However, the CUL4A-knockdown, IL-6, could not induce expression of ZEB1. CHIP assay authenticated that pSTAT3 could bind to CUL4A promoter and worked as their transcription factors. We also demonstrated that IL-6 markedly increased the reporter activity using a luciferase reporter gene containing CUL4A promoter. Finally, silencing CUL4A blocked IL-6-driven invasion in matrigel invasion assay.
  
  
  
  This study proposed that CUL4A played an oncogene role through ZEB1 in IL-6-induced colorectal carcinoma progression.
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. Electronic address: wgren@bjmu.edu.cn.
authors.forename: Weiguo
authors.initials: W
authors.lastname: Ren
authors.affiliation: Surgical Gastroenterology, Xinjiang Medical University Cancer Hospital, Urumqi, Xinjiang, China.
authors.forename: Zhenqiang
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Qinglei
authors.initials: Q
authors.lastname: Zeng
authors.affiliation: Department of Oncology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Han
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Qinglin
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Libin
authors.initials: L
authors.lastname: Jiang
mesh_terms: D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D044842:Cullin Proteins / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D059016:Tumor Microenvironment
chemical_list: C114234:CUL4A protein, human; D044842:Cullin Proteins; C508600:IL6 protein, human; D015850:Interleukin-6; D050796:STAT3 Transcription Factor
keywords: CUL4A; Colorectal cancer; IL-6; ZEB1; pSTAT3