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...
| Autores: | , , , , , , , , , |
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| Tipo de documento: | artigo |
| Estado: | Versão publicada |
| Data de publicação: | 2026 |
| País: | España |
| Recursos: | Fundació Sant Joan de Déu |
| Repositório: | r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu |
| OAI Identifier: | oai:fsjd.fundanetsuite.com:p30071 |
| Acesso em linha: | https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=30071 |
| Access Level: | Acceso aberto |
| Palavra-chave: | LMNA-related dilated cardiomyopathy Biological pathways MicroRNA RNA-sequencing mRNA miRNA-gene interaction |
| Resumo: | 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. |
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