@misc{10481/93225,
year = {2024},
month = {4},
url = {https://hdl.handle.net/10481/93225},
abstract = {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 miRNAseq
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.},
organization = {European Regional Development
Fund (ERDF) Integrated Territorial Initiative (ITI0017_2019)},
organization = {Fundación de Progreso y
Salud PEER (2020-019)},
publisher = {MDPI},
keywords = {Dilated cardiomyopathy},
keywords = {Ischemic cardiomyopathy},
keywords = {Volume overload},
title = {Unraveling the Etiology of Dilated Cardiomyopathy through Differential miRNA–mRNA Interactome},
doi = {10.3390/biom14050524},
author = {Bonet, Fernando and Hernández Torres, Francisco and Ramos-Sánchez, Mónica and Quezada-Feijoo, Maribel and Bermúdez-García, Aníbal and Daroca, Tomás and Alonso Villa, Elena and García Padilla, Carlos and Mangas, Alipio and Toro, Rocio},
}