Altered plasma exosome miRNAs and novel potential biomarkers in pediatric fulminant myocarditis
Xinyue Zhang1, Ruling Yang1, Mengjie Ma1
1Department of Pediatric Cardiology, Shandong Provincial Hospital, Shandong University, Jinan, China.
Abstract:
Previous studies have indicated that exosome-mediated intercellular microRNAs (miRNA) can influence fulminant myocarditis (FM) pathogenesis between immune and cardiac cells. This study explored plasma exosome miRNA profile in pediatric FM using a small RNA microarray. As per our analysis, we observed the differential expression of 266 miRNAs, including 197 upregulated and 69 downregulated candidate genes. Differentially expressed mRNAs in pediatric FM patients' peripheral blood mononuclear cells (PBMCs) were intersected with miRNA target genes predicting tools to screen for FM-specific target genes. The hub genes and their biological and mechanistic pathways related to inflammation and/or the immune system were identified. CeRNA networks of lncRNAs, circRNAs, miRNAs, and mRNAs between cardiomyocytes and PBMCs were finally established. Furthermore, we verified that hsa-miR-146a-5p, hsa-miR-23a-3p, and hsa-miR-27a-3p had higher expression levels in exosomes of pediatric FM patients by qRT-PCR, and hsa-miR-146a-5p shown high sensitivities and specificities for FM diagnosis. Overall, the results demonstrate that the exosome miRNAs play a regulatory role between immune and cardiac cells and provide research targets.
Insights
Exosomes carrying microRNAs (miRNAs) impact fulminant myocarditis (FM) development. Plasma exosome miRNA profiles in pediatric FM revealed specific biomarkers, including hsa-miR-146a-5p, offering diagnostic potential.
Area of Science:
- Cardiovascular Research
- Immunology
- Molecular Biology
Background:
- Exosomes mediate intercellular communication via microRNAs (miRNAs), influencing diseases like fulminant myocarditis (FM).
- Understanding miRNA profiles in pediatric FM is crucial for elucidating disease mechanisms.
Purpose of the Study:
- To investigate the plasma exosome miRNA profile in pediatric FM.
- To identify specific miRNA biomarkers and regulatory networks involved in FM pathogenesis.
Main Methods:
- Small RNA microarray analysis of plasma exosomes from pediatric FM patients.
- Bioinformatic analysis to identify differentially expressed miRNAs and target genes.
- Quantitative real-time PCR (qRT-PCR) validation of specific miRNAs.
Main Results:
- Identified 266 differentially expressed miRNAs (197 upregulated, 69 downregulated) in pediatric FM exosomes.
- Established competing endogenous RNA (ceRNA) networks involving lncRNAs, circRNAs, miRNAs, and mRNAs.
- Validated elevated expression of hsa-miR-146a-5p, hsa-miR-23a-3p, and hsa-miR-27a-3p; hsa-miR-146a-5p demonstrated high diagnostic sensitivity and specificity.
Conclusions:
- Plasma exosome miRNAs play a significant regulatory role between immune and cardiac cells in pediatric FM.
- Specific exosome miRNAs, particularly hsa-miR-146a-5p, serve as potential diagnostic biomarkers for FM.
- This study provides novel research targets for understanding and treating pediatric FM.
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