UBE2T promotes proliferation via G2/M checkpoint in hepatocellular carcinoma
Authors Liu LL, Zhu JM, Yu XN, Zhu HR, Shi X, Bilegsaikhan E, Guo HY, Wu J, Shen XZ
Received 23 January 2019
Accepted for publication 19 August 2019
Published 13 September 2019 Volume 2019:11 Pages 8359—8370
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 4
Editor who approved publication: Dr Beicheng Sun
Li-Li Liu,1,2,* Ji-Min Zhu,1,2,* Xiang-Nan Yu,1,2 Hai-Rong Zhu,1,2 Xuan Shi,1,2 Enkhnaran Bilegsaikhan,1,2 Hong-Ying Guo,1,2 Jian Wu,1–3 Xi-Zhong Shen1–3
1Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai 200032, People’s Republic of China; 2Shanghai Institute of Liver Diseases, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai 200032, People’s Republic of China; 3Department of Medical Microbiology and Parasitology, Ministry of Education/National Health Commission/Chinese Academy of Medical Sciences, Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Xi-Zhong Shen
Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, 180 Fenglin Road, Shanghai 200032, People’s Republic of China
Tel +86 216 404 1990
Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, 138 Yixue Yuan Road, P.O. Box 228, Shanghai 200032, People’s Republic of China
Tel +86 21 5423 7705
Background: Growing evidence suggests that the ubiquitin-proteasome system is involved in the pathogenesis and recurrence of hepatocellular carcinoma (HCC); yet, little is known about the role of ubiquitin-conjugating enzyme E2T (UBE2T) in HCC.
Materials and methods: UBE2T levels were detected in HCC tissues and hepatoma cell lines using quantitative reserve transcriptase-polymerase chain reaction and Western blot analysis. Next, the changes of phenotypes after UBE2T knockdown or overexpression were evaluated using in vitro methods. Finally, the mechanism of UBE2T in HCC was tested using ex vivo and in vivo methods.
Results: In the present study, we reported that UBE2T mRNA and protein levels were significantly upregulated in HCC tissues compared to adjacent non-tumor tissues. Additionally, suppression of UBE2T expression inhibited proliferation, colony formation, tumorigenesis, migration, and invasion of hepatoma cells, whereas UBE2T overexpression led to the opposite outcomes. Moreover, suppression of UBE2T expression resulted in an increase in G2/M phase and a decrease in the percentage of cells in G1 phase, which indicated a cell cycle arrest at the G2/M phase. In contrast, the percentage of cells in G2/M phase decreased following UBE2T overexpression. Further study indicated that UBE2T regulated the G2/M transition by modulating cyclin B1 and cyclin-dependent kinase 1.
Conclusion: Taken together, the findings of the present study uncover biological functions of UBE2T in hepatoma cells, and delineate preliminary molecular mechanisms of UBE2T in modulating HCC development and progression.
Keywords: hepatocellular carcinoma, UBE2T, ubiquitination, cell cycle
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