Related Experiment Video
Updated: Jun 25, 2025
Tissue-specific miRNA Expression Profiling in Mouse Heart Sections Using In Situ Hybridization
Published on: September 15, 2018
Unraveling the Etiology of Dilated Cardiomyopathy through Differential miRNA-mRNA Interactome
Fernando Bonet1,2, Francisco Hernandez-Torres3, Mónica Ramos-Sánchez4,5
1Medicine Department, School of Medicine, University of Cádiz (UCA), 11003 Cádiz, Spain.
Insights
This study reveals distinct gene and microRNA (miRNA) signatures in volume overload cardiomyopathy (VCM) versus ischemic cardiomyopathy (ICM), identifying novel miRNA-mRNA interactions and pathways crucial for understanding dilated cardiomyopathy (DCM) development.
Area of Science:
- Cardiovascular Biology
- Molecular Genetics
- Biochemistry
Background:
- Dilated cardiomyopathy (DCM) presents a common phenotype across diverse etiologies, necessitating a deeper understanding of underlying pathogenetic mechanisms.
- MicroRNAs (miRNAs) are recognized as critical regulators in cardiovascular diseases, yet their specific roles in different DCM subtypes remain largely uncharacterized.
Purpose of the Study:
- To identify distinct gene and miRNA expression profiles in volume overload cardiomyopathy (VCM) and ischemic cardiomyopathy (ICM).
- To elucidate novel miRNA-mRNA interaction networks and signaling pathways implicated in the pathogenesis of VCM and ICM.
Main Methods:
- Application of mRNA sequencing (mRNA-seq) and miRNA sequencing (miRNA-seq) on myocardial biopsies from VCM and ICM patients.
- Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses for differentially expressed genes (DEGs).
- Identification and validation of miRNA-mRNA interactions using correlation analysis, target prediction, qRT-PCR, and luciferase assays.
Main Results:
- Identification of 112 differentially expressed mRNAs and five dysregulated miRNAs between VCM and ICM.
- DEGs were enriched in pathways associated with extracellular matrix, mitochondrial respiration, cardiac muscle contraction, and fatty acid metabolism (VCM vs. ICM).
- Negative enrichment observed for immune-response-related pathways, including JAK-STAT and NF-kappa B signaling.
- Four significant miRNA-mRNA interactions were identified: miR-218-5p targeting DDX6, TTC39C, and SEMA4A; and miR-494-3p targeting SGMS2.
Conclusions:
- The study presents novel miRNA-mRNA interaction networks and signaling pathways specific to VCM and ICM.
- These findings offer significant insights into the molecular mechanisms driving the development of these distinct forms of dilated cardiomyopathy.
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 miRNA-seq 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.
