Department of Pediatric Cardiology, Shandong Provincial Hospital, Shandong University, Jinan, China.
Department of Pediatric Cardiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
Genomics. 2023 May;115(3):110622. doi: 10.1016/j.ygeno.2023.110622. Epub 2023 Apr 14.
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.
先前的研究表明，外泌体介导的细胞间 microRNAs（miRNA）可以影响免疫细胞和心肌细胞之间暴发性心肌炎（FM）的发病机制。本研究使用小 RNA 微阵列探讨了儿科 FM 患者血浆外泌体 miRNA 谱。根据我们的分析，我们观察到 266 个 miRNA 的差异表达，包括 197 个上调和 69 个下调的候选基因。儿科 FM 患者外周血单个核细胞（PBMC）中的差异表达 mRNA 与 miRNA 靶基因预测工具进行交叉筛选，以筛选出 FM 特异性靶基因。确定与炎症和/或免疫系统相关的关键基因及其生物学和机制途径。最后，在心肌细胞和 PBMC 之间建立了 lncRNA、circRNA、miRNA 和 mRNA 的 ceRNA 网络。此外，我们通过 qRT-PCR 验证了 hsa-miR-146a-5p、hsa-miR-23a-3p 和 hsa-miR-27a-3p 在儿科 FM 患者外泌体中的表达水平较高，hsa-miR-146a-5p 对 FM 诊断具有较高的灵敏度和特异性。总体而言，这些结果表明外泌体 miRNAs 在免疫细胞和心肌细胞之间发挥调节作用，并为研究提供了新的靶点。
