Methylome-driven regulation of miRNA expression and its relationship to cardiac dysfunction in idiopathic dilated...

Idiopathic dilated cardiomyopathy (iDCM) is a multifactorial disease with a complex pathogenesis involving diverse molecular mechanisms. Among these, epigenetic mechanisms, including both DNA methylation and microRNAs (miRNAs)-mediated regulation, play an important role in determining the disease phenotype. However, the interplay between the DNA methylome and the miRNA transcriptome in iDCM remains largely unexplored.

We conducted a cross-cohort multiomic integrative analysis of left ventricular (LV) tissue samples from iDCM patients and control (CNT) donors. DNA methylation profiling was performed using the Infinium MethylationEPIC BeadChip, whereas ncRNA-seq was used to assess transcriptomic changes.

We identified a subset of three miRNAs exhibiting both differential methylation in their promoter regions and differential expression in their primary and mature forms. Notably, the miRNA hsa-miR-433-3p (r = 0.671, p < 0.01), which is involved in fibrotic pathways, appear to be significantly correlated with the left ventricular ejection fraction (LVEF), an established echocardiographic marker of cardiac function.

This study enhances our understanding of the epigenetic mechanisms shaping the miRNA transcriptomic landscape in iDCM, suggesting potential roles for these miRNAs in cardiac dysfunction and myocardial fibrosis.