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Ubiquitin-conjugating enzyme E2T knockdown suppresses hepatocellular tumorigenesis via inducing cell cycle arrest and apoptosis

Authors
  • Guo, Jian
  • Wang, Mu
  • Wang, Jun-Ping
  • Wu, Chang-Xin
Type
Published Article
Journal
World Journal of Gastroenterology
Publisher
Baishideng Publishing Group Inc
Publication Date
Nov 21, 2019
Volume
25
Issue
43
Pages
6386–6403
Identifiers
DOI: 10.3748/wjg.v25.i43.6386
PMID: 31798276
PMCID: PMC6881511
Source
PubMed Central
Keywords
License
Green

Abstract

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.

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