Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 28, 2015; 21(28): 8588-8604
Published online Jul 28, 2015. doi: 10.3748/wjg.v21.i28.8588
Overexpression of chaperonin containing TCP1, subunit 3 predicts poor prognosis in hepatocellular carcinoma
Xiao Cui, Zhi-Ping Hu, Zhao Li, Peng-Ji Gao, Ji-Ye Zhu
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
Xiao Cui, Zhi-Ping Hu, Zhao Li, Peng-Ji Gao, Ji-Ye Zhu, Beijing Key Surgical Basic Research Laboratory of Liver Cirrhosis and Liver Cancer, Peking University People’s Hospital, Beijing 100044, China
Author contributions: Cui X and Hu ZP contributed equally to this work; Cui X, Hu ZP, Li Z and Zhu JY designed the research; Gao PJ collected the clinical data; Cui X and Hu ZP performed the research; Cui X and Li Z contributed analytic tools and analyzed the data; Cui X and Zhu JY wrote the paper.
Supported by Beijing Key Laboratory Special Fund, No. Z141107004414042.
Institutional review board statement: This study was reviewed and approved by Institutional Review Board of Peking University People’s Hospital, Beijing, China.
Conflict-of-interest statement: The authors declare no conflict of interest in this study.
Data sharing statement: No additional data was available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Ji-Ye Zhu, MM, Professor, Department of Hepatobiliary Surgery, Peking University People’s Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing 100044, China. gandanwk@vip.sina.com
Telephone: +86-10-88324175 Fax: +86-10-68310585
Received: April 7, 2015
Peer-review started: April 8, 2015
First decision: May 18, 2015
Revised: June 3, 2015
Accepted: July 3, 2015
Article in press: July 3, 2015
Published online: July 28, 2015
Abstract

AIM: 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.

CONCLUSION: 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.

Keywords: Hepatocellular carcinoma, Chaperonin Containing TCP1, Subunit 3, Cell growth, Invasion, Prognosis

Core tip: Hepatocellular carcinoma (HCC) is a lethal disease and it is difficult to evaluate prognosis and manage the disease. This study showed that overexpression of chaperonin containing TCP1, subunit 3 (CCT3) in the nuclei of cancerous cells was an independent risk factor for the prognosis of HCC patients and was associated with tumor histological type and microvascular invasion. CCT3 affects activation of the interleukin-6/signal transducer and activator of transcription 3 signal pathway in vitro. CCT3 could play an essential role in the progression of HCC and might represent a prognostic biomarker in patients with HCC after hepatectomy.