ArticleNeuro-oncology2024
Metabolic modulation of histone acetylation mediated by HMGCL activates the FOXM1/β-catenin pathway in glioblastoma.
Article in Neuro-oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 25 citations in OpenAlex.
- Redox Regulation in Glioblastoma: Mechanisms, Biomarkers, and Therapeutic Implications.International journal of molecular sciences · 2026Review
- SIRT6-Mediated Deacetylation of ATF3 Promotes Silica-Induced Lung Fibrosis by Enhancing its Nuclear Import via Binding to Importin α.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Integrated proteomic and single-nucleus transcriptomic profiling identifies prognostic markers and therapeutic targets in glioblastoma.Discover oncology · 2026Article
- A FoxM1/Smad4 positive feedback loop promotes pancreatic cancer progression.Cell death & disease · 2026Article
- ZNF460 inhibits HMGCL and promotes PI3K pathway in colon cancer.Translational cancer research · 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
- Dermal Fibroblast Senescence: The Central Hub of Skin Aging-From Intrinsic Dysfunction to Microenvironmental Remodeling.International journal of molecular sciences · 2026Review
- Single-cell and multi-omics integrative modeling identifies mitochondrial gene HSPE1 as a therapeutic target in osteosarcoma.Journal of translational medicine · 2026Article
- Acetylation modification in malignant progression and therapeutic resistance of gliomas.Frontiers in cell and developmental biology · 2026Review
- Molecular alterations in MAPK/ERK, β-Catenin/Wnt, and PI3K/mTOR pathways in adenomatoid odontogenic tumor.Journal of applied oral science : revista FOB · 2026Article
- The embedding of stress: mitophagy as a mechanism for the central nervous system (CNS) programming and lifelong disease vulnerability.Frontiers in cell and developmental biology · 2026Review
- Identification of potential biomarkers associated with mitochondrial oxidative stress in idiopathic pulmonary arterial hypertension via bioinformatic and experimental analysis.Scientific reports · 2025Article
- MicroRNA strand ratio disarray promotes temozolomide resistance in glioblastoma.Cellular & molecular biology letters · 2025Article
- Dendritic cells: understanding ontogeny, subsets, functions, and their clinical applications.Molecular biomedicine · 2025Review
- HADHA-mediated regulation of JAK/STAT3 signaling in glioblastoma: a metabolic-epigenetic axis.Cell death discovery · 2025Article
- Unveiling the Maze: Branched-Chain Amino Acids Fueling the Dynamics of Cancer Metabolism and Progression.Cancers · 2025Review
- Research advances in branched-chain amino acid metabolism in tumors.Molecular and cellular biochemistry · 2025Review
- HMGCL activates autophagy in osteosarcoma through β-HB mediated inhibition of the PI3K/AKT/mTOR signaling pathway.Journal of translational medicine · 2025Article
- Comprehensive Overview of Ketone Bodies in Cancer Metabolism: Mechanisms and Application.Biomedicines · 2025Review
Corrections and comments
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Authors and funding
21 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundAltered branched-chain amino acid (BCAA) metabolism modulates epigenetic modification, such as H3K27ac in cancer, thus providing a link between metabolic reprogramming and epigenetic change, which are prominent hallmarks of glioblastoma multiforme (GBM). Here, we identified mitochondrial 3-hydroxymethyl-3-methylglutaryl-CoA lyase (HMGCL), an enzyme involved in leucine degradation, promoting GBM progression and glioma stem cell (GSC) maintenance.
methodsIn silico analysis was performed to identify specific molecules involved in multiple processes. Glioblastoma multiforme cells were infected with knockdown/overexpression lentiviral constructs of HMGCL to assess malignant performance in vitro and in an orthotopic xenograft model. RNA sequencing was used to identify potential downstream molecular targets.
resultsHMGCL, as a gene, increased in GBM and was associated with poor survival in patients. Knockdown of HMGCL suppressed proliferation and invasion in vitro and in vivo. Acetyl-CoA was decreased with HMGCL knockdown, which led to reduced NFAT1 nuclear accumulation and H3K27ac level. RNA sequencing-based transcriptomic profiling revealed FOXM1 as a candidate downstream target, and HMGCL-mediated H3K27ac modification in the FOXM1 promoter induced transcription of the gene. Loss of FOXM1 protein with HMGCL knockdown led to decreased nuclear translocation and thus activity of β-catenin, a known oncogene. Finally, JIB-04, a small molecule confirmed to bind to HMGCL, suppressed GBM tumorigenesis in vitro and in vivo.
conclusionsChanges in acetyl-CoA levels induced by HMGCL altered H3K27ac modification, which triggers transcription of FOXM1 and β-catenin nuclear translocation. Targeting HMGCL by JIB-04 inhibited tumor growth, indicating that mediators of BCAA metabolism may serve as molecular targets for effective GBM treatment.
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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.