Transcriptomic and methylation analysis of left ventricular tissue identified 58 differentially expressed miRNAs in iDCM, with 37 containing differentially methylated positions in their promoters.
Observational (n=43)
DNA methylation in promoter regions may contribute to the dysregulation of key miRNAs, such as hsa-miR-122-5p and hsa-miR-133a-5p, in idiopathic dilated cardiomyopathy.
Abstract Background/Introduction Idiopathic dilated cardiomyopathy (iDCM) is a leading cause of heart failure (HF), driven by a complex aetiology involving numerous molecular mechanisms. Among these, DNA methylation has been identified as a key epigenetic mechanism linked to iDCM progression through the regulation of coding gene expression. Recent studies in other pathologies suggest that DNA methylation also influences non-coding regions of the genome, including those encoding microRNAs (miRNAs) critical regulators of disease pathways. This additional layer of epigenetic regulation provides new insights into the pathogenic mechanisms underlying iDCM. Purpose To investigate the relationship between DNA methylation patterns and the expression profile of miRNAs in patients with iDCM, providing insights into the potential epigenetic mechanisms contributing to the disease phenotype. Methods A transcriptomic study based on ncRNA-seq technology was conducted using left ventricular (LV) tissue samples from 8 control (CNT) individuals and 20 iDCM patients (85% male; mean age: 50.0 ± 11.0 years). Additionally, the methylome was analysed using the Illumina Infinitum MethylationEPIC BeadChip in 9 CNT LV tissue samples and 6 iDCM LV tissue samples (83.3% male, 16.7% female; mean age: 56.5 ± 6.4 years). A linear model was applied to obtain beta values (β) for the detected cytosine-guanine (CpG) sites. To localize the transcription start sites (TSS) for the miRNA of interest, the miRStart 2.0 database was used, and a ± 2000 nucleotide range was considered to define the promoter region. Results The transcriptomic analysis identified the expression of 762 miRNAs, of which 58 were differentially expressed between groups. Among them, 20 miRNAs were downregulated, while 38 were upregulated in DCM LV tissue samples compared to CNT. Methylation analysis of the promoter regions of these differentially expressed miRNAs revealed that 37 out of the 58 contained at least one differentially methylated position (DMP) within the selected promoter region. Notably, hsa-miR-122-5p and hsa-miR-133a-5p, previously described as actors in the pathogenic process of iDCM, exhibited a significant variation in methylation at CpG position within their promoter regions, indicating a potential epigenetic mechanism contributing to its dysregulation in iDCM. Conclusion(s) This study highlights the role of DNA methylation in regulating miRNA expression in iDCM. The identification of differentially methylated promoter regions in key miRNAs, including hsa-miR-122-5p and hsa-miR-133a-5p, suggests that epigenetic modifications may contribute to miRNA dysregulation in iDCM.
Martinez et al. (Sat,) conducted a observational in Idiopathic dilated cardiomyopathy (iDCM) (n=43). Transcriptomic and methylome analysis vs. Control individuals was evaluated on Differentially expressed miRNAs and differentially methylated positions in promoter regions. Transcriptomic and methylation analysis of left ventricular tissue identified 58 differentially expressed miRNAs in iDCM, with 37 containing differentially methylated positions in their promoters.