Abstract
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.
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Data availability
Data transparency is guaranteed. The datasets generated during and/or analyzed during the current study are available in the supplemental material. The original mRNA and miRNA sequencing data from mice at 50 weeks are available in the NCBI BioProject database under accession number PRJNA1232038.
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Acknowledgements
We thank the European Molecular Biology Laboratory GeneCore, Genomics Core Facility (Heidelberg, Germany) staff for processing our samples.
Funding
This work was supported by grants in the framework of the European Regional Development Fund (ERDF) Integrated Territorial Initiative (ITI0017-2019) and Foundation Progreso y Salud PEER (2020-019). This work was supported by funds from Spanish Ministry of Economy and Competitiveness PID2022-140047OB-C21.; the Institute of Health Carlos III (project IMPaCT-Data, exp. IMP/00019), co-funded by the European Union, European Regional Development Fund (ERDF, “A way to make Europe”). This work was also supported by Bosch i Aymerich Foundation. IDIBGI and Fundació Sant Joan de Dèu are a “CERCA Programme / Generalitat de Catalunya”.
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All authors have read and approved the submission of the manuscript. Author Contributions: RT, JAGR, OC and AM conceived the experiments; JCC, FBM and IPdCI recruited the subjects. JCC, FBM and IPdCI conducted the experiments, and IPdCI, BVM and PSZ analyzed the results. JCC, FBM, GSB, OC, and RT wrote the manuscript. All authors reviewed the manuscript.
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Córdoba-Caballero, J., Martínez, F.B., Campuzano, O. et al. An integrative approach to identify novel miRNA-mRNA interaction networks in LMNA-cardiomyopathy. Sci Rep (2026). https://doi.org/10.1038/s41598-026-36439-9
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DOI: https://doi.org/10.1038/s41598-026-36439-9
