H2AC19 acts as a novel regulator of angiogenesis to promote the progression of lung adenocarcinoma

Background: Angiogenesis is a significant character of lung adenocarcinoma (LUAD) and is an important reason leading to high mortality rates of LUAD patients. Identification of potential therapeutic targets for regulating angiogenesis has clinical importance for the treatment of LUAD. Methods: We constructed a prognostic risk model based on hypoxia- and angiogenesis-associated genes using bioinformatics analysis. CRISPR/Cas9-mediated knockout, overexpression and truncation mutants of H2AC19 and patient-derived organoid (PDO) models were used to assess H2AC19 function in LUAD. RNA-seq, ChIP-seq and molecular docking were performed to explore the underlying mechanism. Results: It was found that the level of H2AC19 was increased in human samples with LUAD, which was positively correlated with angiogenesis and clinical stage, negatively correlated with patient prognosis. Knockout of H2AC19 suppressed angiogenesis and tumor growth in vitro and in vivo models, and reduced HUVEC proliferation, migration, and tube formation in LUAD cell/HUVEC coculture model. Mechanistically, H2AC19 promoted angiogenesis, at least in part through p300/EGR1/MMP-1 signaling pathway. Conclusions: Collectively, our findings provide new insights into the pivotal role of H2AC19 in regulating angiogenesis, indicating that H2AC19 might serve as an attractive therapeutic target for LUAD.