ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
ASH2L-K312-Lac Stimulates Angiogenesis in Tumors to Expedite the Malignant Progression of Hepatocellular Carcinoma.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed.
- Covalent allosteric inhibition of AARS1 lactyltransferase.Nature communications · 2026Article
- The METTL3/TRIM37 axis contributes to the progression of non-alcoholic fatty liver disease by promoting CAV1 degradation.Molecular and cellular biochemistry · 2026Article
- Targeting lactylation in hepatocellular carcinoma: Mechanistic insights and therapeutic opportunities (Review).International journal of molecular medicine · 2026Review
- HNRNPU K181 Lactylation Drives Cervical Cancer Growth by Upregulating PHGDH and Reprogramming Serine Metabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Protein lactylation in cancer: principles, programmes and therapeutic opportunities.Molecular cancer · 2026Review
- PIK3CB depletion restores immunosurveillance and enhances radioactive iodine response in hepatocellular carcinoma.Cell biology and toxicology · 2026Article
- Epigenetic Alterations in Hepatocellular Carcinoma: Mechanisms and Biomarkers for Precision Therapy.Cancers · 2026Review
- Single-cell reanalysis highlights the MIF-PTGDR axis as a candidate immunoregulatory program in hepatocellular carcinoma.Discover oncology · 2026Article
- GATA2 promotes hepatitis B virus-associated hepatocellular carcinoma development by regulating AURKA.Archives of microbiology · 2026Article
- Lactylation enzymes in cancer: Mechanisms and novel therapeutic approaches (Review).Oncology letters · 2026Review
- Targeting Lactate and Lactylation in Cancer Metabolism and Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Methyltransferase-Like 14 Promotes the Angiogenesis of Hepatocellular Carcinoma via Targeting Vascular Endothelial Growth Factor A.Cancer reports (Hoboken, N.J.) · 2026Article
- Multi-omics insights for deciphering prognosis-related T cell subsets in hepatocellular carcinoma.Clinical and translational medicine · 2026Article
- H4K5 lactylation - ENO2 loop drives glycolysis and HCC progression.JHEP reports : innovation in hepatology · 2026Article
- Lactylation and targeted therapy resistance in hepatocellular carcinoma.Clinical epigenetics · 2026Review
- TDP-43 Dysfunction Causes Hyper-Lactate State, Increased AARS1 Expression and Enhanced Protein Lactylation.Neurotoxicity research · 2026Article
- ADAM15 promotes the progression and metastasis of hepatocellular carcinoma by activating the JNK/p38 pathway.Scientific reports · 2026Article
- Comprehensive pan-cancer analysis of AARS1, a newly identified lactyltransferase in human cancers.Cancer cell international · 2026Article
- Multi-omics analysis and experimental validation uncovers prognosis significance of IKBIP in patients with hepatocellular carcinoma: a multicenter cohort study.BMC gastroenterology · 2026Article
- Lactylation as a metabolic-epigenetic switch in cancer: dual roles in cell death resistance and therapeutic vulnerability.Cell death & disease · 2026Review
Corrections and comments
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Authors and funding
15 authors.
Funding
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Abstract
Hepatocellular carcinoma (HCC) is a common malignant tumor. However, the role of lactic acid-modified proteins in its pathogenesis is unclear. This study determines the distribution of a novel post-translational modification-protein lactylation-in HCC to identify potential targets and obtain mechanistic insights into this disease. Using high-throughput proteomics, lysine 312 lactylation (K312-lac) of the Set1/Ash2 histone methyltransferase complex subunit (ASH2L) is revealed as a candidate for further investigation. Subsequently, alanyl-tRNA synthetase 1 (AARS1) and histone deacetylase 1 (HDAC1) are shown to mediate lactylation modification of ASH2L. In vivo experiments demonstrate that ASH2L-K312-lac promotes HCC malignant progression and is positively correlated with tumor microvessel density, and vascular endothelial growth factor A (VEGFA) is identified as the key mediator in ASH2L-K312-lac-induced angiogenesis. High-throughput sequencing reveals ASH2L-K312-lac enrichment in the genome regions encoding VEGFA, facilitating targeted recruitment of the mixed lineage leukemia complex to these loci and enhancing VEGFA expression through synergistic activation of enhancers and promoters. Finally, clinical sample analyses and robust in vivo preclinical experiments identify ASH2L-K312-lac as a promising therapeutic target for clinical application. These findings provide a theoretical foundation for the clinical translation of ASH2L-K312-lac-based treatment approaches, offering potential advancements in HCC diagnosis and treatment.
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