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UBE2L3, a susceptibility gene that plays oncogenic role in hepatitis B-related hepatocellular carcinoma.

Authors
  • Liu, Yao1
  • Song, Ci2
  • Ni, Hengli1
  • Jiao, Weijuan1
  • Gan, Wenjuan3
  • Dong, Xiaoqiang4
  • Liu, Jibin5
  • Zhu, Liguo6
  • Zhai, Xiangjun6
  • Hu, Zhibin2
  • Li, Jianming1
  • 1 Department of Pathology, Medical College of Soochow University, Suzhou, China. , (China)
  • 2 Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, School of Public Health, Nanjing Medical University, Nanjing, China. , (China)
  • 3 Department of Pathology, The First Affiliated Hospital of Soochow University, Suzhou, China. , (China)
  • 4 Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China. , (China)
  • 5 Department of Hepatobiliary Surgery, Nantong Tumor Hospital, Nantong, China. , (China)
  • 6 Department of Infection Diseases, Jiangsu Province Center for Disease Prevention and Control, Nanjing, China. , (China)
Type
Published Article
Journal
Journal of Viral Hepatitis
Publisher
Wiley (Blackwell Publishing)
Publication Date
Nov 01, 2018
Volume
25
Issue
11
Pages
1363–1371
Identifiers
DOI: 10.1111/jvh.12963
PMID: 29969176
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Previously, we identified UBE2L3 as a susceptibility gene for chronic hepatitis B virus (HBV) infection through genome-wide association study. Here, we analysed the association between genetic variants of UBE2L3 and the susceptibility to HBV-related hepatocellular carcinoma (HCC) and further explored its role in HCC. This case-control study included 1344 subjects who cleared HBV, 1560 HBV carriers and 1057 HBV-related HCC patients. Two single nucleotide polymorphisms (SNPs) were genotyped, including rs2266959 and rs4821116. Logistic regression analysis was performed to compute the odds ratio (OR) and 95% confidence interval (CI). We further analysed the expression of UBE2L3 and its association with pathological features based on The Cancer Genome Atlas (TCGA) data and our tissue microarray. Proliferation and migration assays were performed in hepatoma cell lines with or without UBE2L3 knockdown. Further RNA-seq analysis was performed to explore the underlying oncogenic mechanism. The variant genotypes of rs4821116 in UBE2L3 were associated with decreased risk for HCC and chronic HBV infection. Moreover, based on both TCGA and our tissue microarray data, higher levels of UBE2L3 expression were correlated with higher tumour grade, advanced tumour stage and poor survival. In vitro analysis revealed that UBE2L3 may promote hepatocyte proliferation and migration. RNA-seq analysis showed that UBE2L3 was inversely correlated with CDKN2B, a negative regulator of cell cycle, and CLDN1, loss of which may promote cancer metastasis. In conclusion, UBE2L3 may also be a susceptibility gene in HBV-related HCC, and it may promote HCC proliferation and migration by negatively regulating CDKN2B and CLDN1. © 2018 John Wiley & Sons Ltd.

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