ArticleGastroenterology2011
Hepatitis B virus core promoter mutations contribute to hepatocarcinogenesis by deregulating SKP2 and its target, p21.
Article in Gastroenterology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 2 of them syntheses that pooled it.
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Who cites it
44 citing papers in PubMed, 2 syntheses or guidelines pooled it, 75 citations in OpenAlex.
- Different nucleos(t)ide analogs in resected hepatitis B virus-associated hepatocellular carcinoma: a systematic review.Frontiers in pharmacology · 2025Pooled it
- The association between hepatitis B mutants and hepatocellular carcinoma: A meta-analysis.Medicine · 2017Pooled it
- Precore/core mutation relatedness to viral reactivation in patients undergoing targeted therapy for hepatitis B virus-related hepatocellular carcinoma.World journal of biological chemistry · 2026Review
- The oncogenic role of hepatitis B virus X gene in hepatocarcinogenesis: recent updates.Exploration of targeted anti-tumor therapy · 2024Review
- Hepatitis B virus X protein induces ALDH2 ubiquitin-dependent degradation to enhance alcoholic steatohepatitis.Gastroenterology report · 2023Article
- Review on hepatitis B virus precore/core promoter mutations and their correlation with genotypes and liver disease severity.World journal of hepatology · 2022Review
- Whole genome analysis of hepatitis B virus before and during long-term therapy in chronic infected patients: Molecular characterization, impact on treatment and liver disease progression.Frontiers in microbiology · 2022Article
- The Effects and Underlying Mechanisms of Hepatitis B Virus X Gene Mutants on the Development of Hepatocellular Carcinoma.Frontiers in oncology · 2022Article
- Perturbation ofInternational journal of molecular sciences · 2021Article
- Lost Small Envelope Protein Expression from Naturally Occurring PreS1 Deletion Mutants of Hepatitis B Virus Is Often Accompanied by Increased HBx and Core Protein Expression as Well as Genome Replication.Journal of virology · 2021Article
- A Noncoding Variant Near PPP1R3B Promotes Liver Glycogen Storage and MetS, but Protects Against Myocardial Infarction.The Journal of clinical endocrinology and metabolism · 2021Article
- Paeoniflorin inhibits cell viability and invasion of liver cancer cells via inhibition of Skp2.Oncology letters · 2020Article
- Review
- High possibility of hepatocarcinogenesis in HBV genotype C1 infected Cambodians is indicated by 340 HBV C1 full-genomes analysis from GenBank.Scientific reports · 2019Article
- Article
- The interaction of hepatitis B virus with the ubiquitin proteasome system in viral replication and associated pathogenesis.Virology journal · 2019Review
- Correlations between cytokines produced by T cells and clinical-virological characteristics in untreated chronic hepatitis B patients.BMC infectious diseases · 2019Article
- Contribution of Hepatitis B Virus Infection to the Aggressiveness of Primary Liver Cancer: A Clinical Epidemiological Study in Eastern China.Frontiers in oncology · 2019Article
- Upregulation of kinesin family member 4A enhanced cell proliferation via activation of Akt signaling and predicted a poor prognosis in hepatocellular carcinoma.Cell death & disease · 2018Article
- Regulation of Akt/FoxO3a/Skp2 Axis Is Critically Involved in Berberine-Induced Cell Cycle Arrest in Hepatocellular Carcinoma Cells.International journal of molecular sciences · 2018Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsClinical studies have associated hepatitis B virus core promoter (CP) mutations with an increased risk of hepatocellular carcinoma. The CP region overlaps with the HBV X (HBx) gene, which has been implicated in hepatocarcinogenesis. The cyclin kinase inhibitor p21WAF1/CIP1 is an important regulator of cell cycle progression and proliferation. We determined whether HBx mutants that result from mutations in the CP deregulate p21 and these processes.
methodsWe constructed a series of HBx mutants with changes in the CP region that correspond to A1762T/G1764A (TA), T1753A, T1768A, or a combination of these (combo) and expressed them, along with wild-type HBx under control of its endogenous promoter, in primary human hepatocytes (PHHs) and HepG2 cells. We then analyzed the effects of CP mutations on expression and degradation of p21 and the effects on cell cycle progression and proliferation.
resultsThe combo mutant decreased levels of p21 and increased cyclin E expression in PHHs and HepG2 cells. The combo mutant, but not HBx with single or double CP mutations, accelerated p21 degradation in HepG2 cells. The combo mutant increased expression of S-phase kinase-associated protein 2 (SKP2) in PHHs and Huh7 cells. Silencing of SKP2 abrogated the effects of CP mutations on p21 expression. The kinetics of p21 expression correlated with changes in cell cycle distribution. The combo mutant accelerated cell cycle progression; p21 overexpression restored G1 arrest.
conclusionsHBx mutants with changes that correspond to a combination of CP mutations up-regulate SKP2, which then down-regulates p21 via ubiquitin-mediated proteasomal degradation. CP mutations might increase the risk of hepatocellular carcinoma via this pathway.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.