Retrospective Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 28, 2016; 22(16): 4226-4237
Published online Apr 28, 2016. doi: 10.3748/wjg.v22.i16.4226
Eukaryotic elongation factor-1α 2 knockdown inhibits hepatocarcinogenesis by suppressing PI3K/Akt/NF-κB signaling
Fu-Nan Qiu, Yi Huang, Dun-Yan Chen, Feng Li, Yan-An Wu, Wen-Bing Wu, Xiao-Li Huang
Fu-Nan Qiu, Yi Huang, Dun-Yan Chen, Feng Li, Yan-An Wu, Wen-Bing Wu, Xiao-Li Huang, Provincial Clinical College, Fujian Medical University, Fuzhou 350001, Fujian Province, China
Fu-Nan Qiu, Department of Hepatobiliary Surgery, Fujian Provincial Hospital, Fuzhou 350001, Fujian Province, China
Yi Huang, Dun-Yan Chen, Yan-An Wu, Wen-Bing Wu, Xiao-Li Huang, Department of Clinical Laboratory, Fujian Provincial Hospital, Fuzhou 350001, Fujian Province, China
Feng Li, Department of Pathology, Fujian Provincial Hospital, Fuzhou 350001, Fujian Province, China
Author contributions: Qiu FN and Huang Y contributed equally to this study; Qiu FN and Huang Y were the guarantors of integrity of the entire study, study concepts, study design, definition of intellectual content, literature research, experimental studies, data acquisition, data analysis, and statistical analysis; Chen DY, Li F and Wu WB participated in experimental studies and data acquisition; Chen DY, Wu YA and Huang XL participated in data analysis and statistical analysis; Huang Y and Wu YA prepared the manuscript; Huang Y edited and reviewed the manuscript; all authors read and approved the final manuscript.
Supported by the Middle-Young Age Backbone Talent Cultivation Program of Fujian Health System, No. 2013-ZQN-JC-2; and Key Projects of Science and Technology Plan of Fujian Province, No. 2014Y0009.
Institutional review board statement: This study was approved by the Ethics Committee of Fujian Provincial Hospital and conducted in accordance with the Declaration of Helsinki and international guidelines.
Informed consent statement: All patients provided signed informed consent.
Conflict-of-interest statement: All the authors declare that they have no conflict of interest.
Data sharing statement: No additional data 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: Yi Huang, PhD, Provincial Clinical College, Fujian Medical University, No. 134 Dong Street, Fuzhou 350001, Fujian Province, China. yihuang8070@sina.com
Telephone: +86-591-88216378 Fax: +86-591-87532356
Received: November 10, 2015
Peer-review started: November 10, 2015
First decision: December 21, 2015
Revised: January 13, 2016
Accepted: January 30, 2016
Article in press: January 30, 2016
Published online: April 28, 2016
Processing time: 160 Days and 23.5 Hours
Abstract

AIM: To assess the impact of eukaryotic elongation factor 1 alpha 2 (eEF1A2) on hepatocellular carcinoma (HCC) cell proliferation, apoptosis, migration and invasion, and determine the underlying mechanisms.

METHODS: eEF1A2 levels were detected in 62 HCC tissue samples and paired pericarcinomatous specimens, and the human HCC cell lines SK-HEP-1, HepG2 and BEF-7402, by real-time PCR and immunohistochemistry. Experimental groups included eEF1A2 silencing in BEL-7402 cells with lentivirus eEF1A2-shRNA (KD group) and eEF1A2 overexpression in SK-HEP-1 cells with eEF1A2 plasmid (OE group). Non-transfected cells (control group) and lentivirus-based empty vector transfected cells (NC group) were considered control groups. Cell proliferation (MTT and colony formation assays), apoptosis (Annexin V-APC assay), cell cycle (DNA ploidy assay), and migration and invasion (Transwell assays) were assessed. Protein levels of PI3K/Akt/NF-κB signaling effectors were evaluated by Western blot.

RESULTS: eEF1A2 mRNA and protein levels were significantly higher in HCC cancer tissue samples than in paired pericarcinomatous and normal specimens. SK-HEP-1 cells showed lower eEF1A2 mRNA levels; HepG2 and BEL-7402 cells showed higher eEF1A2 mRNA levels, with BEL-7402 cells displaying the highest amount. Efficient eEF1A2 silencing resulted in reduced cell proliferation, migration and invasion, increased apoptosis, and induced cell cycle arrest. The PI3K/Akt/NF-κB signaling pathway was notably inhibited. Inversely, eEF1A2 overexpression resulted in promoted cell proliferation, migration and invasion.

CONCLUSION: eEF1A2, highly expressed in HCC, is a potential oncogene. Its silencing significantly decreases HCC tumorigenesis, likely by inhibiting PI3K/Akt/NF-κB signaling.

Keywords: Hepatocellular carcinoma; Carcinogenesis; Eukaryotic elongation factor 1 alpha 2; Proliferation; PI3K/Akt/NF-κB signaling pathway

Core tip: Whether eukaryotic elongation factor 1 alpha 2 (eEF1A2) affects hepatocellular carcinoma (HCC) biology is largely unknown. In this study, eEF1A2 mRNA and protein levels were significantly higher in HCC cancer tissue samples than in paired control specimens. Efficient eEF1A2 silencing resulted in reduced cell proliferation, migration and invasion, increased apoptosis, and induced cell cycle arrest; the PI3K/Akt/NF-κB signaling pathway was notably inhibited. Inversely, eEF1A2 overexpression resulted in promoted cell proliferation, migration and invasion. Our findings indicate that eEF1A2 is a potential oncogene, whose silencing significantly decreases HCC tumorigenesis, likely by inhibiting PI3K/Akt/NF-κB signaling.