ArticleHepatology (Baltimore, Md.)2016
A new HIF-1α/RANTES-driven pathway to hepatocellular carcinoma mediated by germline haploinsufficiency of SART1/HAF in mice.
Article in Hepatology (Baltimore, Md.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 44 citations in OpenAlex.
- Partial Depletion of SART1 Selectively Induces Mitotic Defects and Cell Death in Cancer Cells.Genes to cells : devoted to molecular & cellular mechanisms · 2026Article
- Chemokines and chemokine receptors in metabolic dysfunction-associated steatohepatitis: pathogenic mechanisms and clinical implications.Cellular & molecular biology letters · 2026Review
- SART1 modulates poly-(ADP-ribose) chain accumulation and PARP1 chromatin localization.iScience · 2024Article
- Review
- The Role of Type 2 Diabetes Mellitus-Related Risk Factors and Drugs in Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2024Review
- Hollow Mesoporous Silica Nanoparticles for Dual Chemo-starvation Therapy of Hepatocellular Carcinoma.Pharmaceutical research · 2023Article
- Inflammatory processes involved in NASH-related hepatocellular carcinoma.Bioscience reports · 2023Review
- Liver regeneration biology: Implications for liver tumour therapies.World journal of clinical oncology · 2021Review
- Profiles of messenger RNAs and MicroRNAs in hypoxia-induced hepatic stellate cells.Annals of translational medicine · 2021Article
- Tumor Immune Microenvironment and Immunosuppressive Therapy in Hepatocellular Carcinoma: A Review.International journal of molecular sciences · 2021Review
- Suppressing Sart1 to modulate macrophage polarization by siRNA-loaded liposomes: a promising therapeutic strategy for pulmonary fibrosis.Theranostics · 2021Article
- Hepatic macrophages in liver homeostasis and diseases-diversity, plasticity and therapeutic opportunities.Cellular & molecular immunology · 2021Review
- Immunobiology and immunotherapy of HCC: spotlight on innate and innate-like immune cells.Cellular & molecular immunology · 2021Review
- Hypoxia-inducible factors and innate immunity in liver cancer.The Journal of clinical investigation · 2020Review
- Immunological distinctions between nonalcoholic steatohepatitis and hepatocellular carcinoma.Experimental & molecular medicine · 2020Review
- Modulating the Crosstalk between the Tumor and Its Microenvironment Using RNA Interference: A Treatment Strategy for Hepatocellular Carcinoma.International journal of molecular sciences · 2020Review
- Dioxin-like and non-dioxin-like PCBs differentially regulate the hepatic proteome and modify diet-induced nonalcoholic fatty liver disease severity.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2020Article
- The role of the innate immune system in the development and treatment of hepatocellular carcinoma.Hepatic oncology · 2020Review
- lncRNAs Are Involved in Sevoflurane Anesthesia-Related Brain Function Modulation through Affecting Mitochondrial Function and Aging Process.BioMed research international · 2020Article
- From bench to bed: the tumor immune microenvironment and current immunotherapeutic strategies for hepatocellular carcinoma.Journal of experimental & clinical cancer research : CR · 2019Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
unlabelledThe hypoxia-inducible factor (HIF), HIF-1, is a central regulator of the response to low oxygen or inflammatory stress and plays an essential role in survival and function of immune cells. However, the mechanisms regulating nonhypoxic induction of HIF-1 remain unclear. Here, we assess the impact of germline heterozygosity of a novel, oxygen-independent ubiquitin ligase for HIF-1α: hypoxia-associated factor (HAF; encoded by SART1). SART1(-/-) mice were embryonic lethal, whereas male SART1(+/-) mice spontaneously recapitulated key features of nonalcoholic steatohepatitis (NASH)-driven hepatocellular carcinoma (HCC), including steatosis, fibrosis, and inflammatory cytokine production. Male, but not female, SART1(+/-) mice showed significant up-regulation of HIF-1α in circulating and liver-infiltrating immune cells, but not in hepatocytes, before development of malignancy. Additionally, Kupffer cells derived from male, but not female, SART1(+/-) mice produced increased levels of the HIF-1-dependent chemokine, regulated on activation, normal T-cell expressed and secreted (RANTES), compared to wild type. This was associated with increased liver-neutrophilic infiltration, whereas infiltration of lymphocytes and macrophages were not significantly different. Neutralization of circulating RANTES decreased liver neutrophilic infiltration and attenuated HCC tumor initiation/growth in SART1(+/-) mice.
conclusionThis work establishes a new tumor-suppressor role for HAF in immune cell function by preventing inappropriate HIF-1 activation in male mice and identifies RANTES as a novel therapeutic target for NASH and NASH-driven HCC.
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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.