We explored N6-methyladenosine (m6A) RNA methylation as one of the gene regulatory mechanisms in heart failure (HF) biology. Understanding the different physiological mechanisms will facilitate the prevention and individualized treatment of HF. The Gene Expression Omnibus (GEO) database served as the source of the data. In GSE116250, differential analysis between ischemic cardiomyopathy (ICM), dilated cardiomyopathy (DCM) and controls yielded differentially expressed m6A regulators. Differential analysis between HF and controls in GSE131296 identifies m6A-modified genes and then performs enrichment analysis. Protein-protein interaction (PPI) network analysis was performed for the differentially expressed ICM- or DCM-associated genes in GSE116250 and GSE55296, respectively. Finally, the diagnostic genes for ICM and DCM were predicted using receiver operating characteristic (ROC) curve. YTHDC1, HNRNPC and HNRNPA2B1 were significantly downregulated in GSE116250 in DCM and ICM compared with controls. A total of 195 genes were identified in GSE131296 as subject to m6A alteration. These genes may play a role in HF through the MAPK signaling pathway and p53 signaling pathway. PPI network analysis identified CCL5, CXCR4 and CCL2 as key genes for ICM and IL-6 as a key gene for DCM. Through ROC curves, we identified m6A-modified APLP1, KLF2 as potential diagnostic genes for ICM, and m6A-modified FGF7, FREM1 and C14orf132 as potential diagnostic genes for DCM. Our findings support m6A modifying mechanisms in HF etiology that contribute to the treatment of HF. Thus, our data suggest that m6A methylation may be an interesting target for therapeutic intervention.
Keywords: Heart failure; diagnosis; dilated cardiomyopathy; ischemic cardiomyopathy; m6A methylation modification.