ArticlePloS one2014
HBx inhibits CYP2E1 gene expression via downregulating HNF4α in human hepatoma cells.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 25 citations in OpenAlex.
- HBV/HCV coinfection and anti-tuberculosis drug-induced liver injury: from risk assessment and exploration of mechanisms to preventive considerations.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2026Review
- Hepatitis B virus protein X promotes survival and loss of hepatocyte identity in a differentiated human liver organoid system.Cell death and differentiation · 2026Article
- Overexpression ofBioMed research international · 2025Article
- Hepatocyte-Targeted Lipid Nanoparticle Delivery of HERC2 Plasmid Controls Drug-Induced Hepatotoxicity by Limiting β-Catenin-Regulated CYP2E1 Expression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Whole-Genome Resequencing Revealed Selective Signatures for Growth Traits in Hu and Gangba Sheep.Genes · 2024Article
- Generation and Characterization of CYP2E1-Overexpressing HepG2 Cells to Study the Role of CYP2E1 in Hepatic Hypoxia-Reoxygenation Injury.International journal of molecular sciences · 2023Article
- Prediction of hepatocellular carcinoma risk in patients with chronic liver disease from dynamic modular networks.Journal of translational medicine · 2021Article
- The Hepatitis B Virus Interactome: A Comprehensive Overview.Frontiers in microbiology · 2021Review
- Acetaldehyde suppresses HBV-MHC class I complex presentation on hepatocytes via induction of ER stress and Golgi fragmentation.American journal of physiology. Gastrointestinal and liver physiology · 2020Article
- Transcriptional Regulation in Non-Alcoholic Fatty Liver Disease.Metabolites · 2020Review
- [Carcinoembryonic type specific markers and liver cancer immunotherapy].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2020Review
- Suppression of Hepatocyte Nuclear Factor 4 α by Long-term Infection of Hepatitis B Virus Contributes to Tumor Cell Proliferation.International journal of molecular sciences · 2020Article
- Role of hepatocyte nuclear factor 4-alpha in gastrointestinal and liver diseases.World journal of gastroenterology · 2019Review
- Acetaldehyde suppresses the display of HBV-MHC class I complexes on HBV-expressing hepatocytes.American journal of physiology. Gastrointestinal and liver physiology · 2019Article
- Urinary and Genetic Biomonitoring of Polycyclic Aromatic Hydrocarbons in Egyptian Coke Oven Workers: Associations between Exposure, Effect, and Carcinogenic Risk Assessment.The international journal of occupational and environmental medicine · 2019Article
- Acrylamide induces HepG2 cell proliferation through upregulation of miR-21 expression.Journal of biomedical research · 2019Article
- Article
- HNF-4α promotes multidrug resistance of gastric cancer cells through the modulation of cell apoptosis.Oncology letters · 2017Article
- Crosstalk of HNF4Acta pharmaceutica Sinica. B · 2016Review
- Cytochrome P450 family members are associated with fast-growing hepatocellular carcinoma and patient survival: An integrated analysis of gene expression profiles.Saudi journal of gastroenterology : official journal of the Saudi Gastroenterology AssociationArticle
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CYP2E1, one of the cytochrome P450 mixed-function oxidases located predominantly in liver, plays a key role in metabolism of xenobiotics including ethanol and procarcinogens. Recently, down-expression of CYP2E1 was found in hepatocellular carcinoma (HCC) with the majority to be chronic hepatitis B virus (HBV) carriers. In this study, we tested a hypothesis that HBx may inhibit CYP2E1 gene expression via hepatocyte nuclear factor 4α (HNF4α). By enforced HBx gene expression in cultured HepG2 cells, we determined the effect of HBx on CYP2E1 mRNA and protein expression. With a bioinformatics analysis, we found a consensus HNF-4α binding sequence located on -318 to -294 bp upstream of human CYP2E1 promoter. Using reporter gene assay and site-directed mutagenesis, we have shown that mutation of this site dramatically decreased CYP2E1 promoter activity. By silencing endogenous HNF-4α, we have further validated knockdown of HNF-4α significantly decreased CYP2E1 expression. Ectopic overexpression of HBx in HepG2 cells inhibits HNF-4α expression, and HNF-4α levels were inversely correlated with viral proteins both in HBV-infected HepG2215 cells and as well as HBV positive HCC liver tissues. Moreover, the HBx-induced CYP2E1 reduction could be rescued by ectopic supplement of HNF4α protein expression. Furthermore, human hepatoma cells C34, which do not express CYP2E1, shows enhanced cell growth rate compared to E47, which constitutively expresses CYP2E1. In addition, the significantly altered liver proteins in CYP2E1 knockout mice were detected with proteomics analysis. Together, HBx inhibits human CYP2E1 gene expression via downregulating HNF4α which contributes to promotion of human hepatoma cell growth. The elucidation of a HBx-HNF4α-CYP2E1 pathway provides novel insight into the molecular mechanism underlining chronic HBV infection associated hepatocarcinogenesis.
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