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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
BACKGROUND
Hepatocellular carcinoma (HCC) is now the most common primary liver malignancy worldwide, and multiple risk factors attribute to the occurrence and development of HCC. Recently, increasing studies suggest that ubiquitin-conjugating enzyme E2T (UBE2T) serves as a promising prognostic factor in human cancers, although the molecular mechanism of UBE2T in HCC remains unclear.
AIM
To investigate the clinical relevance and role of UBE2T in HCC development.
METHODS
UBE2T expression in HCC tissues from the TCGA database and its association with patient survival were analyzed. A lentivirus-mediated strategy was used to knock down UBE2T in HCC cells. qRT-PCR and Western blot assays were performed to check the effect of UBE2T silencing in HCC cells. Cell growth in vitro and in vivo was analyzed by multiparametric high-content screening and the xenograft tumorigenicity assay, respectively. Cell cycle distribution and apoptosis were determined by flow cytometry. The genes regulated by UBE2T were profiled by microarray assay.
RESULTS
UBE2T was overexpressed in HCC tissues compared with paired and non-paired normal tissues. High expression of UBE2T predicted a poor overall survival in HCC patients. In vitro, lentivirus-mediated UBE2T knockdown significantly reduced the viability of both SMMC-7721 and BEL-7404 cells. In vivo, the xenograft tumorigenesis of SMMC-7721 cells was largely attenuated by UBE2T silencing. The cell cycle was arrested at G1/S phase in SMMC-7721 and BEL-7404 cells with UBE2T knockdown. Furthermore, apoptosis was increased by UBE2T knockdown. At the molecular level, numerous genes were dysregulated after UBE2T silencing, including IL-1B, FOSL1, PTGS2, and BMP6.
CONCLUSION
UBE2T plays an important role in cell cycle progression, apoptosis, and HCC development.
Core tip: Ubiquitin-conjugating enzyme E2T (UBE2T) is a member of the ubiquitin-proteasome family. Although it has been reported that UBE2T promotes the growth of hepatocellular carcinoma (HCC) cells, the role of UBE2T in the HCC cell cycle, apoptosis, and tumorigenesis is unclear. UBE2T was highly expressed in HCC tissues, and its expression was correlated with the survival of HCC patients. Silencing of UBE2T reduced the viability and xenograft tumor growth of HCC cells. Additionally, cell cycle arrest and apoptosis were induced by UBE2T knockdown. Numerous genes were regulated by UBE2T silencing in HCC cells. Therefore, UBE2T is a novel diagnostic and therapeutic target for HCC.
