ArticleActa pharmacologica Sinica2015
Hepatitis B virus X protein promotes human hepatoma cell growth via upregulation of transcription factor AP2α and sphingosine kinase 1.
Article in Acta pharmacologica Sinica, 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, 23 citations in OpenAlex.
- Immunomodulatory Effects of SPHK1 and Its Interaction with TFAP2A in Yellow Drum (International journal of molecular sciences · 2024Article
- Hepatitis B Virus Increases SphK1-S1P Synthesis by Promoting the Availability of the Transcription Factor USF1.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Critical Roles of the Sphingolipid Metabolic Pathway in Liver Regeneration, Hepatocellular Carcinoma Progression and Therapy.Cancers · 2024Review
- Integrative roles of sphingosine kinase in liver pathophysiology.Toxicological research · 2023Review
- Article
- The Hepatitis B Virus Interactome: A Comprehensive Overview.Frontiers in microbiology · 2021Review
- Targeting the SphK-S1P-SIPR Pathway as a Potential Therapeutic Approach for COVID-19.International journal of molecular sciences · 2020Review
- Exploring DNA Methylation Profiles Altered in Cryptogenic Hepatocellular Carcinomas by High-Throughput Targeted DNA Methylation Sequencing: A Preliminary Study for Cryptogenic Hepatocellular Carcinoma.OncoTargets and therapy · 2020Article
- Emerging Connections of S1P-Metabolizing Enzymes with Host Defense and Immunity During Virus Infections.Viruses · 2019Review
- Recent trends in click chemistry as a promising technology for virus-related research.Virus research · 2018Review
- Divergent Role of Sphingosine 1-Phosphate in Liver Health and Disease.International journal of molecular sciences · 2018Review
- Peretinoin, an Acyclic Retinoid, Inhibits Hepatitis B Virus Replication by Suppressing Sphingosine Metabolic Pathway In Vitro.International journal of molecular sciences · 2018Article
- Sphingosine kinase and sphingosine-1-phosphate in liver pathobiology.Critical reviews in biochemistry and molecular biology · 2017Review
- miR-511 promotes the proliferation of human hepatoma cells by targeting the 3'UTR of B cell translocation gene 1 (BTG1) mRNA.Acta pharmacologica Sinica · 2017Article
- The Tumorigenic Effect of Sphingosine Kinase 1 and Its Potential Therapeutic Target.Cancer control : journal of the Moffitt Cancer CenterReview
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimSphingosine kinase 1 (SPHK1) is involved in various cellular functions, including cell growth, migration, apoptosis, cytoskeleton architecture and calcium homoeostasis, etc. As an oncogenic kinase, SPHK1 is associated with the development and progression of cancers. The aim of this study was to investigate whether SPHK1 was involved in hepatocarcinogenesis induced by the hepatitis B virus X protein (HBx).
methodsThe expression of SPHK1 in hepatocellular carcinoma (HCC) tissue and hepatoma cells were measured using qRT-PCR and Western blot analysis. HBx expression levels in hepatoma cells were modulated by transiently transfected with HBx or psi-HBx plasmids. The SPHK1 promoter activity was measured using luciferase reporter gene assay, and the interaction of the transcription factor AP2α with the SPHK1 promoter was studied with chromatin immunoprecipitation assay. The growth of hepatoma cells was evaluated in vitro using MTT and colony formation assays, and in a tumor xenograft model.
resultsA positive correlation was found between the mRNA levels of SPHK1 and HBx in 38 clinical HCC samples (r=+0.727, P<0.01). Moreover, the expression of SPHK1 was markedly increased in the liver cancer tissue of HBx-transgenic mice. Overexpressing HBx in normal liver cells LO2 and hepatoma cells HepG2 dose-dependently increased the expression of SPHK1, whereas silencing HBx in HBx-expressing hepatoma cells HepG2-X and HepG2.2.15 suppressed SPHK1 expression. Furthermore, overexpressing HBx in HepG2 cells dose-dependently increased the SPHK1 promoter activity, whereas silencing HBx in HepG2-X cells suppressed this activity. In HepG2-X cells, AP2α was found to directly interact with the SPHK1 promoter, and silencing AP2α suppressed the SPHK1 promoter activity and SPHK1 expression. Silencing HBx in HepG2-X cells abolished the HBx-enhanced proliferation and colony formation in vitro, and tumor growth in vivo.
conclusionHBx upregulates SPHK1 through the transcription factor AP2α, which promotes the growth of human hepatoma cells.
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