Roles of methyltransferase-like protein 3 and its regulatory genes in intracerebral hemorrhage
MAO Junxiang
GUO Man
ZHAO Guohui
ZHANG Zhenyu
ZHOU Jie
Abstract：Objective To elucidate the mechanisms through which Mettl3 influences the pathophysiological changes following ICH.Methods Utilizing collagenase VII-S and C57bl/6 mice,a model of brain hemorrhage was established and its Mettl3 expression was quantified via qPCR and WB.GSE222968 dataset was harnessed from GEO database to investigate m6A modifications and differential gene expressions,which was complemented by GO and KEGG enrichment analyses,along with assessments of immune cell infiltration and protein interaction networks.WGCNA was employed to pinpoint genes that co-express with Mettl3,intersecting them with differentially expressed genes to identify key players.Lasso regression was then applied to refine the selection of core genes,with subsequent ROC analysis to ascertain their diagnostic potential.Results Post-ICH,Mettl3 expression was found to be elevated,with 5316 m6A-modified genes and 1148 differentially expressed genes implicated in immune biology,alongside significant variations in immune cell infiltration profiles.2077 genes were identified to be co-expressed with Mettl3,narrowing down to the critical genes Apold1,B2m,Cox8b,and Tnnt1 upon intersection with differentially expressed genes.Lasso regression singled out Apold1 and Tnnt1 as pivotal genes,with ROC analysis underscoring the diagnostic significance of Apold1.Conclusions The modulation of Apold1 by Mettl3 serves as a potential biomarker for ICH diagnosis and a target for novel immunotherapeutic strategies.
Keywords：intracerebral hemorrhageN6-methyladenosineMettl3targets for treatment
Publication Date：2025-12-28
Online Publishing Date：2025-12-02(First online date of this platform, not the publication date of the document)
Pages：8( 8-15 )