An integrative approach to identify novel miRNA-mRNA interaction networks in LMNA-cardiomyopathy.

Dilated cardiomyopathy caused by variants in the LMNA gene leads to malignant arrhythmogenic events, faster phenotype progression and high risk of sudden cardiac death. The pathophysiological mechanisms triggering disease progression remains poorly understood. We investigated the mRNA and miRNA tran...

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Detalles Bibliográficos
Autores: Cordoba-Caballero, Jose, Martinez, Fernando Bonet, Campuzano, Oscar, Sarquella-Brugada, Georgia, Perez De Castro, Ignacio, Vilaplana-Marti, Borja, Seoane-Zonjic, Pedro, Mangas, Alipio, Ranea, Juan A. G., Toro, Rocio
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2026
País:España
Institución:Fundació Sant Joan de Déu
Repositorio:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
OAI Identifier:oai:fsjd.fundanetsuite.com:p30071
Acceso en línea:https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=30071
Access Level:acceso abierto
Palabra clave:LMNA-related dilated cardiomyopathy
Biological pathways
MicroRNA
RNA-sequencing
mRNA
miRNA-gene interaction
Descripción
Sumario:Dilated cardiomyopathy caused by variants in the LMNA gene leads to malignant arrhythmogenic events, faster phenotype progression and high risk of sudden cardiac death. The pathophysiological mechanisms triggering disease progression remains poorly understood. We investigated the mRNA and miRNA transcriptome in the myocardial tissue of 50-week-old LMNA(R249W) mice developing dilated cardiomyopathy. We found 2148 genes and 53 miRNAs that were differentially expressed in LMNA(R249W) hearts. Gene ontology and pathway enrichments showed that differentially expressed genes were enriched mainly for fatty acid metabolism, muscle contraction, cell adhesion and dilated cardiomyopathy pathways. The miRNA-mRNA interactions analysis identified 2197 miRNA-target pairs with an anti-correlation between differentially expressed genes and miRNAs. Gene ontology and pathway enrichments revealed that the most significant functions of miRNA targets are mainly related to heart development, cardiac muscle contraction, fatty acid ß-oxidation, cell adhesion and calcium binding pathways, among others. Our study provides new insights into the molecular mechanisms that determine dilated cardiomyopathy due to pathogenic variants in the LMNA gene, and identified several target pairs that are of potential interest for further studies.