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©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
Ubiquitin-conjugating enzyme E2T knockdown suppresses hepatocellular tumorigenesis via inducing cell cycle arrest and apoptosis
Jian Guo, Mu Wang, Jun-Ping Wang, Chang-Xin Wu
Jian Guo, Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Biotechnology, Shanxi University, Taiyuan 030006, Shanxi Province, China
Jian Guo, Department of General Surgery, Shanxi Provincial People’s Hospital, the Affiliated People’s Hospital of Shanxi Medical University, Taiyuan 030012, Shanxi Province, China
Mu Wang, Department of Neurology, Shanxi Provincial People’s Hospital, the Affiliated People’s Hospital of Shanxi Medical University, Taiyuan 030012, Shanxi Province, China
Jun-Ping Wang, Department of Gastroenterology, Shanxi Provincial People’s Hospital, the Affiliated People’s Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
Chang-Xin Wu, The Institutes of Biomedical Sciences, Shanxi University, Taiyuan 03006, Shanxi Province, China
Chang-Xin Wu, Key Laboratory of Molecular Biology and Biochemistry of Ministry of Education, Shanxi University, Taiyuan 030006, Shanxi Province, China
Author contributions: Wu CX designed the research; Guo J performed the majority of experiments and wrote the paper; Wang JP and Wang M coordinated the research.
Institutional review board statement: This study was approved by the ethics committee of The Affiliated People's Hospital of Shanxi Medical University.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of The Affiliated People's Hospital of Shanxi Medical University (IACUC protocol number: 20171236).
Conflict-of-interest statement: No potential conflicts of interest are disclosed.
Data sharing statement: Data are available from the first author at guo10121012@163.com
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
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/
Corresponding author: Chang-Xin Wu, PhD, Professor, The Institutes of Biomedical Sciences, Shanxi University, Taiyuan 030006, Shanxi Province, China.
cxw20@sxu.edu.cn
Telephone: +86-351-4960141 Fax: +86-351-4960123
Received: January 16, 2019
Peer-review started: January 16, 2019
First decision: February 13, 2019
Revised: September 10, 2019
Accepted: September 13, 2019
Article in press: September 13, 2019
Published online: November 21, 2019
Processing time: 309 Days and 18.3 Hours
ARTICLE HIGHLIGHTS
Research background
Hepatocellular carcinoma (HCC) is one of most common malignant tumors with a poor prognosis. Increasing studies indicated that dysregulation of ubiquitin-conjugating enzyme E2T (UBE2T) contributes to the development of human cancers. However, whether UBE2T is involved in the progression of HCC is unclear.
Research motivation
Previous studies have illustrated the critical role of UBE2T in the progression of various tumors, and our study will suggest the role of UBE2T in regulating the occurrence and development of HCC.
Research objectives
To investigate the biological function of UBE2T in HCC cell proliferation and progression in vitro by gain-of-function and loss-of-function strategies, and provides significant insights into the underlying molecular mechanisms of UBE2T involved in the development of HCC, which may contribute to the future research of more effective diagnosis and treatment.
Research methods
The expression of UBE2T in HCC tissues was obtained from The Cancer Genome Atlas database. In vitro experiments using lentivirus-medicated approach were performed to examine cell growth, cell cycle distribution, and apoptosis by CCK8 assay and flow cytometry, respectively. The xenograft tumorigenicity assay was performed to determine the capacity of cell proliferation in vivo. The whole genome expression profile was analyzed by microarray assay.
Research results
In this study, we identified remarkable overexpression of UBE2T in HCC tissues, which closely corrected with a poor overall survival in HCC patients. The results of in vitro experiments suggested a critical role of UBE2T in cell viability, cell cycle, and apoptosis of HCC. In both SMMC-7721 and BEL-7404 cells, the HCC cell proliferation was obviously inhibited, cell cycle was arrested at G1/S phase, and apoptosis was significantly promoted by lentivirus-medicated UBE2T knockdown. Moreover, the growth of SMMC-7721 cells with UBE2T knockdown in xenografts was significantly inhibited in vivo. The microarray assay confirmed that UBE2T silencing contributed to the dysregulation of numerous genes, including IL-1B, FOSL1, PTGS2, and BMP6.
Research conclusions
In conclusion, UBE2T is significantly involved in HCC cell proliferation, cell cycle, and apoptosis.
Research perspectives
Our study may provide a novel potential diagnostic and therapeutic target for HCC intervention.
