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<p>Dilated cardiomyopathy caused by variants in the <i>LMNA</i> 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 <i>LMNA</i><sup><i>R249W</i></sup> mice developing dilated cardiomyopathy. We found 2148 genes and 53 miRNAs that were differentially expressed in <i>LMNA</i><sup><i>R249W</i></sup> 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 β-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 <i>LMNA</i> gene, and identified several target pairs that are of potential interest for further studies.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月24日

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  • José Córdoba-Caballero,
  • Fernando Bonet,
  • Oscar Campuzano,
  • Georgia Sarquella-Brugada,
  • Ignacio Perez de Castro,
  • Borja Vilaplana-Martí,
  • Pedro Seoane-Zonjic,
  • Alipio Mangas,
  • Juan A. G. Ranea,
  • Rocio Toro

摘要

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 LMNAR249W mice developing dilated cardiomyopathy. We found 2148 genes and 53 miRNAs that were differentially expressed in LMNAR249W 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 β-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.