title: Overexpression of chaperonin containing TCP1, subunit 3 predicts poor prognosis in hepatocellular carcinoma.
abstract: OBJECTIVE
  To investigate the value of chaperonin containing TCP1, subunit 3 (CCT3) to predict the prognosis of patients with hepatocellular carcinoma (HCC) and determine its function in HCC progression.
  
  
  METHODS
  CCT3 expression levels were examined in human non-cancerous liver tissues and a variety of HCC cell lines by quantitative real-time PCR and immunoblotting. CCT3 expression was suppressed by small interfering RNA. The effects of reducing CCT3 expression in HCC cells were tested. The 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide (MTT) assay, cell counting experiment, cell cycle assay, apoptosis assay and invasion assay were employed to evaluate cell functions in vitro. Immunohistochemistry was performed on HCC specimens. In addition, CCT3 expression in HCC specimens was also assessed at the protein and mRNA level. Associations between clinicopathological characteristics and prognosis were analyzed, along with the possible mechanisms involved in CCT3's function in HCC progression.
  
  
  RESULTS
  The expression levels of CCT3 mRNA and protein were upregulated in HCC cell lines in contrast to adjacent non-cancerous tissues. Reducing CCT3 expression not only suppressed cell proliferation in cell counts, MTT assay, cell cycle assay and induced cell apoptosis (P < 0.05 vs negative control), but also inhibited the tumor cell invasion capacity in vitro (P < 0.01 vs negative control). Overexpression of CCT3 in the nuclei of cancer cells in HCC specimens (58 of 104 patients, 55.8%) was associated with poor prognosis in HCC patients (3-year survival rate, 55.5% vs 84.2%, P = 0.020) after hepatectomy. Mechanistic analyses showed that signal transducer and activator of transcription 3 (STAT3) activation was decreased even when stimulated by interleukin-6 after knocking down CCT3 in the HepG2 cell line.
  
  
  CONCLUSIONS
  Overexpression of CCT3 in the nuclei of cancerous cells is associated with HCC progression. CCT3 may be a target that affects the activation of STAT3 in HCC.
authors.affiliation: Xiao Cui, Zhi-Ping Hu, Zhao Li, Peng-Ji Gao, Ji-Ye Zhu, Department of Hepatobiliary Surgery, Peking University People's Hospital, Beijing 100044, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Cui
authors.affiliation: Xiao Cui, Zhi-Ping Hu, Zhao Li, Peng-Ji Gao, Ji-Ye Zhu, Department of Hepatobiliary Surgery, Peking University People's Hospital, Beijing 100044, China.
authors.forename: Zhi-Ping
authors.initials: ZP
authors.lastname: Hu
authors.affiliation: Xiao Cui, Zhi-Ping Hu, Zhao Li, Peng-Ji Gao, Ji-Ye Zhu, Department of Hepatobiliary Surgery, Peking University People's Hospital, Beijing 100044, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Li
authors.affiliation: Xiao Cui, Zhi-Ping Hu, Zhao Li, Peng-Ji Gao, Ji-Ye Zhu, Department of Hepatobiliary Surgery, Peking University People's Hospital, Beijing 100044, China.
authors.forename: Peng-Ji
authors.initials: PJ
authors.lastname: Gao
authors.affiliation: Xiao Cui, Zhi-Ping Hu, Zhao Li, Peng-Ji Gao, Ji-Ye Zhu, Department of Hepatobiliary Surgery, Peking University People's Hospital, Beijing 100044, China.
authors.forename: Ji-Ye
authors.initials: JY
authors.lastname: Zhu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D056404:Chaperonin Containing TCP-1 / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D016016:Proportional Hazards Models; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D012307:Risk Factors; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation
chemical_list: C533299:CCT3 protein, human; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D056404:Chaperonin Containing TCP-1
keywords: Cell growth; Chaperonin Containing TCP1, Subunit 3; Hepatocellular carcinoma; Invasion; Prognosis