ArticleHepatology international2023
HMGCL-induced β-hydroxybutyrate production attenuates hepatocellular carcinoma via DPP4-mediated ferroptosis susceptibility.
Article in Hepatology international, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 35 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Metabolic phenotyping combined with transcriptomics metadata fortifies the diagnosis of early-stage Hepatocellular carcinoma.Journal of advanced research · 2025Pooled it
- Dynamic regulation of H3K9 modifications in cancer: pathogenesis and targeted therapies.Biomarker research · 2026Review
- Histone Post-Translational Modifications Regulating Ferroptosis: The Molecular Mechanisms and Disease Associations.Cell biochemistry and function · 2026Review
- β-Hydroxybutyrate Inhibits Angiogenesis, Suppresses Non-Small Cell Lung Cancer Growth, and Enhances Gemcitabine Antitumor Activity.International journal of molecular sciences · 2026Article
- ZNF460 inhibits HMGCL and promotes PI3K pathway in colon cancer.Translational cancer research · 2026Article
- Identification and validation of DPP4 in predicting the prognosis of clear cell RCC.Discover oncology · 2026Article
- PDHA1 enhances resistance to ferroptosis in anoikis-resistant prostate cancer by upregulating AIFM2.Cell death discovery · 2026Article
- TIGAR maintains intestinal epithelial regeneration by stabilizing HMGCL and promoting β-catenin β-hydroxybutyrylation in burn-induced sepsis.Cell death & disease · 2026Article
- Regulation of apoptosis, ferroptosis, and pyroptosis mediated by acetylation.Cell death discovery · 2026Review
- ILF3 Regulates Cell Proliferation and Metastasis by Competitively Antagonizing the Interaction Between HMGCL and USP38 in Hepatocellular Carcinoma.Human mutation · 2026Article
- The critical role of ferroptosis in thyroid cancer development and potential therapeutic implications.Frontiers in oncology · 2026Review
- Time-restricted feeding protects against septic liver injury by reshaping gut microbiota and metabolite 3-hydroxybutyrate.Gut microbes · 2025Article
- β-hydroxybutyrate, a ketone body, suppresses tumor growth, stemness, and invasive phenotypes in non-small cell lung cancer.Cancer biology & therapy · 2025Article
- Important Role of Bacterial Metabolites in Development and Adjuvant Therapy for Hepatocellular Carcinoma.Current oncology (Toronto, Ont.) · 2025Review
- Prognostic Significance of HMGA1 in Hepatocellular Carcinoma: Implications for Tumor Progression and Targeted Therapy.Archives of Iranian medicine · 2025Article
- Epigenetic regulation of iron metabolism and ferroptosis in Parkinson's disease: Identifying novel epigenetic targets.Acta pharmacologica Sinica · 2025Review
- Proteomic and metabolomic analysis of platelet related samples reveals energy metabolism disorders in hepatocellular carcinoma.Journal of translational medicine · 2025Article
- Epigenetic regulation of ferroptosis in gastrointestinal cancers (Review).International journal of molecular medicine · 2025Review
- Trelagliptin Ameliorates Memory Decline in Diabetic Rats through the AMPK/AKT/GSK-3β Pathway in the Cerebral Cortex.ACS omega · 2025Article
- Maladaptive Peripheral Ketogenesis in Schwann Cells Mediated by CBAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMetabolic disorder is an essential characteristic of tumor development. Ketogenesis is a heterogeneous factor in multiple cancers, but the effect of ketogenesis on hepatocellular carcinoma (HCC) is elusive.
methodsWe aimed to explain the role of ketogenesis-related hydroxy-methyl-glutaryl-CoA lyase (HMGCL) on HCC suppression. Expression pattern of HMGCL in HCC specimens was evaluated by immunohistochemistry (IHC). HMGCL was depleted or overexpressed in HCC cells to investigate the functions of HMGCL in vitro and in vivo. The anti-tumor function of HMGCL was studied in subcutaneous xenograft and Trp53
resultsHMGCL depletion promoted HCC proliferation and metastasis, whereas its overexpression reversed this trend. As HMGCL catalyzes β-hydroxy-butyric acid (β-OHB) production, we discovered that HMGCL increased acetylation at histone H3K9, which further promoted the transcription of dipeptidyl peptidase 4 (DPP4), a key protein maintains intracellular lipid peroxidation and iron accumulation, leading to HCC cells vulnerability to erastin- and sorafenib-induced ferroptosis.
conclusionOur study identified a critical role of HMGCL on HCC suppression, of which HMGCL regulated H3K9 acetylation through β-OHB and modulating the expression of DPP4 in a dose-dependent manner, which led to ferroptosis in HCC cells.
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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.