ArticleJournal of virology2015
Activation of ATP citrate lyase by mTOR signal induces disturbed lipid metabolism in hepatitis B virus pre-S2 mutant tumorigenesis.
Article in Journal of virology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 47 citations in OpenAlex.
- Article
- Palmitoylation of glycoproteins under low temperature enhances SVCV replication.PLoS pathogens · 2026Article
- Integrated spatial metabolomics and transcriptomics reveal the molecular landscape of papillary thyroid cancer and its lymph node metastasis.Journal of translational medicine · 2025Article
- Hepatitis B surface antigen: carcinogenesis mechanisms and clinical implications in hepatocellular carcinoma.Experimental hematology & oncology · 2025Review
- Article
- Is There such a Thing as Post-Viral Depression?: Implications for Precision Medicine.Biomolecules & therapeutics · 2024Review
- mTOR Signaling: Roles in Hepatitis B Virus Infection and Hepatocellular Carcinoma.International journal of biological sciences · 2024Review
- Review
- Review
- Article
- The mTOR/PGC-1α/SIRT3 Pathway Drives Reductive Glutamine Metabolism to Reduce Oxidative Stress Caused by ISKNV in CPB Cells.Microbiology spectrum · 2022Article
- [Hepatitis B and C: mechanisms of virus-induced liver pathogenesis and tumorigenesis].Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz · 2022Review
- Targeting ACLY efficiently inhibits SARS-CoV-2 replication.International journal of biological sciences · 2022Article
- mTOR Signaling: The Interface Linking Cellular Metabolism and Hepatitis B Virus Replication.Virologica Sinica · 2021Review
- Envelope Proteins of Hepatitis B Virus: Molecular Biology and Involvement in Carcinogenesis.Viruses · 2021Review
- Review
- Dairy consumption and hepatocellular carcinoma risk.Annals of translational medicine · 2021Review
- From infection to cancer: how DNA tumour viruses alter host cell central carbon and lipid metabolism.Open biology · 2021Review
- TemporalACS omega · 2020Article
- Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
unlabelledThe development of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) has been found to be associated with disturbed lipid metabolism. To elucidate the role of lipid metabolism in HBV tumorigenesis, we investigated the dynamic pattern of lipid metabolism in HBV pre-S2 mutant-induced tumorigenesis. Lipid and gene expression profiles were analyzed in an in vitro culture system and in transgenic mouse livers harboring HBV pre-S2 mutant. The pre-S2 mutant transgenic livers showed a biphasic pattern of lipid accumulation, starting from mild fatty change in early (1 month) transgenic livers, which subsided and then, remarkably, increased in HCC tissues. This biphasic pattern was synchronized with ATP citrate lyase (ACLY) activation. Further analyses revealed that the pre-S2 mutant initiated an endoplasmic reticulum (ER) stress-dependent mammalian target of rapamycin (mTOR) signalling cascade. The pre-S2 mutant-induced mTOR signal activated the sterol regulatory element binding transcription factor 1 (SREBF1) to upregulate ACLY, which then activated the fatty acid desaturase 2 (FADS2), mediated through ACLY-dependent histone acetylation. Such an ER stress-dependent mTOR signal cascade also is important for the proliferation of hepatocytes in vitro and is further validated in HBV-related HCC tissues. IMPORTANCE: Aberrations of lipid metabolism frequently occur in chronic HBV infection. Our results provide a potential mechanism of disturbed lipid metabolism in HBV pre-S2 mutant-induced tumorigenesis, which should be valuable for the design of HCC chemoprevention in high-risk HBV carriers.
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