Abstract:Aim To analyze the correlation between N6-methyladenosine (m6A) and ferroptosis in acute myocardial infarction (AMI). Methods Two microarray datasets GSE34198 and GSE59867 was explored from GEO database. Both AMI and control samples were analyzed for differentially expressed genes. GO, KEGG, and GSVA analysis of the screened differential genes was performed using R. Machine learning was used to screen ferroptosis associated genes for DRA, GBM, LASSO and randomForest characteristic genes. The expression data of the core ferroptosis gene and m6A-related genes were analyzed by Pearson correlation analysis, and the m6A modified genes and ferroptosis associated genes with strong correlation were screened. Finally, 10 cases of AMI and 10 control whole blood samples from the Fifth Affiliated Hospital of Xinjiang Medical University were collected, and the expression of related genes was verified by RT-qPCR and Western blot. Results 431 common differentially expressed genes were extracted from two datasets, GO and KEGG analysis showed that these genes were mainly enriched in TNF signaling pathway, FoxO signaling pathway and B cell receptor signaling pathway. The enrichment pathways of differentially expressed genes by GSVA were cuproptosis, netotic cell death, entotic cell death, alkaliptosis and ferroptosis. The characteristic genes of ferroptosis associated genes were screened by machine learning, and 19 core ferroptosis associated genes were screened from them. The expression data of ferroptosis associated genes and m6A-related genes were analyzed by Pearson correlation analysis. LRPPRC-IREB2, LRPPRC-ATG5, YTHDC2-IREB2, HNRNPA2B1-IREB2 and YTHDC2-ATG5 were the most correlated top five genes. The results of RT-qPCR and Western blot showed that the gene expression levels of LRPPRC, YTHDC2, HNRNPA2B1, IREB2 and ATG5 were significantly lower than those of the control group (P<0.001), which was consistent with the gene expression in the database. Conclusion m6A methylation is associated with ferroptosis in AMI. By regulating m6A methylation-related genes, ferroptosis in AMI can be regulated. It provides a new idea for the further study of the pathogenesis of the disease.