ArticleDigestive diseases and sciences2015
Hepatitis B Virus Core Promoter A1762T/G1764A (TA)/T1753A/T1768A Mutations Contribute to Hepatocarcinogenesis by Deregulating Skp2 and P53.
Article in Digestive diseases and sciences, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 22 citations in OpenAlex.
- HBX Multi-Mutations Combined With Traditional Screening Indicators to Establish a Nomogram Contributes to Precisely Stratify the High-Risk Population of Hepatocellular Carcinoma.Cancer medicine · 2025Article
- Predicting Hepatocellular Carcinoma Risk in Chronic Hepatitis B Patients Receiving Finite Periods of Antiviral Therapy.Cancers · 2023Article
- The role of hepatitis B virus genome variations in HBV-related HCC: effects on host signaling pathways.Frontiers in microbiology · 2023Review
- Genetic diversity, haplotype analysis, and prevalence of Hepatitis B virus MHR mutations among isolates from Kenyan blood donors.PloS one · 2023Article
- Pathogenicity and virulence of Hepatitis B virus.Virulence · 2022Review
- The mutations frequency of enhancer II/HBx regions of hepatitis B virus in acutely infected Iranian patients: a cross-sectional study.Iranian journal of microbiology · 2022Article
- Molecular pathways in viral hepatitis-associated liver carcinogenesis: An update.World journal of clinical cases · 2021Review
- Impact of Hepatitis B Virus Genetic Variation, Integration, and Lymphotropism in Antiviral Treatment and Oncogenesis.Microorganisms · 2020Review
- Pro-oncogenic, intra host viral quasispecies in Diffuse large B cell lymphoma patients with occult Hepatitis B Virus infection.Scientific reports · 2019Article
- Article
- Rottlerin exerts its anti-tumor activity through inhibition of Skp2 in breast cancer cells.Oncotarget · 2016Article
- HBx mutations promote hepatoma cell migration through the Wnt/β-catenin signaling pathway.Cancer science · 2016Article
- Overview of hepatitis B virus mutations and their implications in the management of infection.World journal of gastroenterology · 2016Review
- Rottlerin exhibits anti-cancer effect through inactivation of S phase kinase-associated protein 2 in pancreatic cancer cells.American journal of cancer research · 2016Article
- Molecular mechanism of hepatitis B virus X protein function in hepatocarcinogenesis.World journal of gastroenterology · 2015Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
aimHepatitis B virus core promoter (CP) mutations can increase risk of hepatocellular carcinoma. The CP region overlaps with the HBV X (HBx) gene, which has been associated with hepatocarcinogenesis. The cyclin kinase inhibitor P53 is an important regulator of cell cycle progression. We determined whether HBx mutants that result from mutations in the CP deregulate P53.
methodsA HBx combination (combo) mutant with changes in the CP region that corresponded to A1762T/G1764A (TA), T1753A, and T1768A was constructed and expressed in L-02 and Hep3B cells. The effects of CP mutations on expression and degradation of P53, and the effects on cell cycle progression and proliferation were analyzed.
resultsThe combo mutant decreased levels of P53 and increased cyclin D1 expression, accelerated P53 degradation in L-02 cells, accelerated cell cycle progression, and increased expression of S-phase kinase-associated protein 2 (Skp2) in L-02 and Hep3B cells. Silencing of Skp2 abrogated the effects of CP mutations on P53 expression. The kinetics of P53 expression correlated with changes in cell cycle distribution.
conclusionsThe HBx mutant with a combination of CP mutations can up-regulate Skp2, which then down-regulates P53 via ubiquitin-mediated proteasomal degradation, increasing the risk of hepatocellular carcinoma.
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