biostudies-literatureUnknown12(40)Han HHepatocellular 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 deAdvanced science (Weinheim, Baden-Wurttemberg, Germany)e09477https://www.ebi.ac.uk/biostudies/studies/S-EPMC12561209biostudies-literatureASH2L-K312-Lac Stimulates Angiogenesis in Tumors to Expedite the Malignant Progression of Hepatocellular Carcinoma.PMC12561209Ma LGu XXia SZhu HCheng XYin HWang SZhang YHan HLiu CZhao DWang YZhu RYuan YfalseASH2L-K312-Lac Stimulates Angiogenesis in Tumors to Expedite the Malignant Progression of Hepatocellular Carcinoma.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 de2025-01-01T00:00:00Z2025 Oct2026-06-05T09:29:51.618Z2026-05-15T03:12:17.113ZS-EPMC125612094072644110.1002/advs.202509477