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<b>Background:<\/b> Oxymatrine executes a therapeutic effect on malignant phenotype tumor cells; nevertheless, the mechanisms of oxymatrine in lung adenocarcinoma (LUAD) require further exploration. Here, the aims of our study are to unveil the effect of oxymatrine and methyltransferase 3 (METTL3) on LUAD tumorigenesis, and reveal the mechanism of METTL3 mediated N6-methyladenosine (m<sup>6<\/sup>A) modification to stabilize Lysine acetyltransferase 2A (KAT2A) expression.\n\n<b>Methods:<\/b> The roles of oxymatrine and METTL3 in LUAD cells, such as survival, migration, and invasion ability, were evaluated via CCK8, colony formation, and transwell experiments. The levels of METTL3 and KAT2A in LUAD cells were analyzed utilizing western blotting and qRT-PCR. Moreover, xenograft model in nude mice was conducted to evaluate oxymatrine's role <i>in vivo<\/i>. The regulatory relationship between METTL3 and KAT2A was clarified utilizing Me-RIP, qRT-PCR, and western blotting assays.\n\n<b>Results:<\/b> Oxymatrine decreased the survival, migration, and invasive ability, and delayed the growth of tumors of LUAD. Inversely, upregulating METTL3 facilitated LUAD cells malignancy and partly abolished oxymatrine's anti-tumor effect. Moreover, KAT2A was mediated by METTL3 to enhance KAT2A m<sup>6<\/sup>A modification and expression in LUAD cells. Furthermore, oxymatrine diminished KAT2A expression through suppression of METTL3.\n\n<b>Conclusion:<\/b> Oxymatrine, an anti-tumor component in LUAD, reduces KAT2A expression via restraining METTL3 levels in a m<sup>6<\/sup>A method. Oxymatrine-METTL3-m<sup>6<\/sup>A-KAT2A may be a potential therapeutic network for LUAD.<\/p>","DOI":"10.1615\/critrevimmunol.2026065687","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T16:37:15Z","timestamp":1784047035000},"page":"79-91","source":"Crossref","is-referenced-by-count":0,"title":["Oxymatrine Attenuates Lung Adenocarcinoma Tumorigenesis via METTL3-Mediated the m6A Modification of KAT2A"],"prefix":"10.1615","volume":"46","author":[{"given":"Zhuxia","family":"Nie","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"613","reference":[{"key":"1","doi-asserted-by":"crossref","unstructured":"Denisenko TV, Budkevich IN, Zhivotovsky B. Cell death-based treatment of lung adenocarcinoma. Cell Death Dis. 2018;9(2):117.","DOI":"10.1038\/s41419-017-0063-y"},{"key":"2","doi-asserted-by":"crossref","unstructured":"Oberndorfer F, Mullauer L. 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