RT journal article
T1 Unraveling the Etiology of Dilated Cardiomyopathy through Differential miRNA–mRNA Interactome
A1 Bonet Martínez, Fernando
A1 Hernandez-Torres, Francisco
A1 Ramos-Sánchez, Mónica
A1 Quezada-Feijoó, Maribel
A1 Bermúdez García, Anibal Jesús
A1 Alonso Villa, Elena
A1 García-Padilla, Carlos
A1 Mangas Rojas, Alipio
A1 Toro Cebada, Rocío
A2 Cirugía
A2 Medicina
K1 dilated cardiomyopathy
K1 etiology
K1 ischemic cardiomyopathy
K1 microRNA
K1 RNA sequencing
K1 volume overload
AB Dilated cardiomyopathy (DCM) encompasses various acquired or genetic diseases sharing a common phenotype. The understanding of pathogenetic mechanisms and the determination of the functional effects of each etiology may allow for tailoring different therapeutic strategies. MicroRNAs (miRNAs) have emerged as key regulators in cardiovascular diseases, including DCM. However, their specific roles in different DCM etiologies remain elusive. Here, we applied mRNA-seq and miRNA-seq to identify the gene and miRNA signature from myocardial biopsies from four patients with DCM caused by volume overload (VCM) and four with ischemic DCM (ICM). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were used for differentially expressed genes (DEGs). The miRNA–mRNA interactions were identified by Pearson correlation analysis and miRNA target-prediction programs. mRNA-seq and miRNA-seq were validated by qRT-PCR and miRNA–mRNA interactions were validated by luciferase assays. We found 112 mRNAs and five miRNAs dysregulated in VCM vs. ICM. DEGs were positively enriched for pathways related to the extracellular matrix (ECM), mitochondrial respiration, cardiac muscle contraction, and fatty acid metabolism in VCM vs. ICM and negatively enriched for immune-response-related pathways, JAK-STAT, and NF-kappa B signaling. We identified four pairs of negatively correlated miRNA–mRNA: miR-218-5p-DDX6, miR-218-5p-TTC39C, miR-218-5p-SEMA4A, and miR-494-3p-SGMS2. Our study revealed novel miRNA–mRNA interaction networks and signaling pathways for VCM and ICM, providing novel insights into the development of these DCM etiologies.
PB Multidisciplinary Digital Publishing Institute (MDPI)
SN 2218-273X
YR 2024
FD 2024
LK http://hdl.handle.net/10498/33668
UL http://hdl.handle.net/10498/33668
LA eng
DS Repositorio Institucional de la Universidad de Cádiz
RD 10-nov-2026