title: Inhibition of Csn3 expression induces growth arrest and apoptosis of hepatocellular carcinoma cells.
abstract: OBJECTIVE
  Csn3 (or CSN3) encodes the third subunit of an eight-subunit complex, the COP9 signalosome (CSN), which acts as a protein kinase and a deneddylase in mammalian cells. Previous studies have shown that Csn3 is essential for maintenance of cell proliferation in the mouse embryonic epiblast and associated with the tumorigenesis process in osteosarcoma. However, its correlation with hepatocellular carcinoma (HCC) has not been explored yet.
  
  
  METHODS
  The expression of Csn3 in HCC (n = 30), cirrhosis (n = 30), and normal tissues (n = 30) was detected using immunohistochemical analysis. The impacts of lentivirus-mediated inhibition of Csn3 on HCC cells were detected using MTT, BrdU incorporation assay, and flow cytometric analysis. In addition, the colony formation and tumor growth ability in nude mice were detected to define the role of Csn3 in tumorigenesis.
  
  
  RESULTS
  Knockdown of Csn3 expression in HCC cell lines (SMMC-7721 and Hep3B) significantly inhibits the tumor growth both in vitro and in vivo. Further investigation indicates that this growth inhibition effect may be mediated through cell cycle arrest in G0/G1 phase and inductions of pro-apoptotic proteins BIK and Caspase-8. In addition, knockdown of Csn3 expression evidently suppresses tumor growth in a xenograft nude mice model.
  
  
  CONCLUSIONS
  Collectively, this study demonstrates Csn3 as an oncogene that regulates the tumorigenesis process in HCC cells.
authors.affiliation: Department of Infectious Diseases, Sixth People's Hospital, Shanghai Jiaotong University, Yishan Road 600, Shanghai 200233, China.
authors.forename: Yong-sheng
authors.initials: YS
authors.lastname: Yu
authors.forename: Zheng-hao
authors.initials: ZH
authors.lastname: Tang
authors.forename: Qing-chun
authors.initials: QC
authors.lastname: Pan
authors.forename: Xiao-hua
authors.initials: XH
authors.lastname: Chen
authors.forename: Xue-ni
authors.initials: XN
authors.lastname: Liu
authors.forename: Guo-qing
authors.initials: GQ
authors.lastname: Zang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D000075686:COP9 Signalosome Complex; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000235:genetics; D045744:Cell Line, Tumor; D005260:Female; D005434:Flow Cytometry; D016193:G1 Phase; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009687:Nuclear Proteins / Q000235:genetics*; D011494:Protein Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins; D016192:Resting Phase, Cell Cycle; D023041:Xenograft Model Antitumor Assays
chemical_list: C000618791:Cops3 protein, mouse; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D011494:Protein Kinases; D000075686:COP9 Signalosome Complex