title: STAT1 inhibits human hepatocellular carcinoma cell growth through induction of p53 and Fbxw7.
abstract: BACKGROUND
  Aberrant STAT1 signaling is observed in human hepatocellular carcinoma (HCC) and has been associated with the modulation of cell proliferation and survival. However, the role of STAT1 signaling in HCC and its underlying mechanism remain elusive.
  
  
  METHODS
  We transiently transfected pcDNA3.1-STAT1 and STAT1 siRNA into SMMC7721 and HepG2 cells. Western blot and qRT-PCR examined the expression of protein and RNA of target genes. Cell viability was assessed using MTT assay, and cell cycle and apoptosis were analyzed by flow cytometry.
  
  
  RESULTS
  We found that STAT1 overexpression increased protein expression of p53 and Fbxw7, and downregulated the expression of cyclin A, cyclin D1, cyclin E, CDK2, Hes-1 and NF-κB p65. These changes led to growth inhibition and induced G0/G1 cell cycle arrest and apoptosis in SMMC7721 and HepG2 cells. Conversely, ablation of STAT1 had the opposite effect on p53, Fbxw7, Hes-1, NF-κB p65, cyclin A, cyclin D1, cyclin E and CDK2, and improved the viability of SMMC7721 and HepG2 cells.
  
  
  CONCLUSIONS
  Our data indicate that STAT1 exerts tumor-suppressive effects in hepatocarcinogenesis through induction of G0/G1 cell cycle arrest and apoptosis, and may provide a basis for the design of new therapies for the intervention of HCC in the clinic.
authors.affiliation: Department of Laboratory Medicine, School of Medicine, Taizhou University, Taizhou, 318000 Zhejiang China.
authors.forename: Jiayu
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Pathogenobiology, Daqing Branch of Harbin Medical University, Daqing, 163319 China.
authors.forename: Haihe
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Endocrinology of Fifth Hospital of Daqing, Daqing, 163714 China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pathogenobiology, Daqing Branch of Harbin Medical University, Daqing, 163319 China.
authors.forename: Shishun
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Pathology, School of Medicine, Zhejiang University, Hangzhou, 310058 China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
keywords: Apoptosis; Cell cycle arrest; HCC; HepG2; SMMC7721; STAT1