ASH2L-K312-Lac Stimulates Angiogenesis in Tumors to Expedite the Malignant Progression of Hepatocellular Carcinoma.

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 de

SUBMITTER: Han H 

PROVIDER: S-EPMC12561209 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature