Nie Xiang, He Mengying, Wang Jin, Chen Peng, Wang Feng, Lai Jinsheng, Li Chenze, Yu Ting, Zuo Houjuan, Cui Guanglin, Miao Kun, Jiang Jiangang, Wang Dao Wen, Chen Chen
Division of Cardiology and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Mol Ther Methods Clin Dev. 2020 May 12;17:1079-1087. doi: 10.1016/j.omtm.2020.05.005. eCollection 2020 Jun 12.
Circulating microRNAs (miRNAs) are potential biomarkers in various diseases. However, whether they could serve as biomarkers for human adult fulminant myocarditis (FM) is unknown. Circulating miRNA expression profiles were detected by microarray analysis and validated by quantitative real-time PCR arrays. Meanwhile, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was used to determine the critical roles of these circulating miRNAs in FM. Moreover, correlation analysis was employed between miRNAs and the parameters of cardiac functions in FM. Finally, the sensitivity and specificity of circulating long non-coding RNA (lncRNA) expression in FM diagnosis were evaluated using receiver operating characteristic curve analysis. Both microarray and quantitative real-time PCR analysis showed that the expression of miR-4763-3p and miR-4281 were upregulated in the plasma of FM at the onset, and their levels were restored as the clinical symptom recovered. The predicted target genes of miR-4763-3p and miR-4281 are involved in several pathways, mainly inflammatory and cardiac injury response. Moreover, the miRNAs enrichment was negatively correlated with the severity of FM. In addition, the expression levels of circulating miR-4763-3p were unchanged in myocardial infarction (MI) patients but showed high sensitivity and specificity for FM diagnosis. This study provides a global profile of circulating miRNAs in patients with FM, among which miR-4763-3p could serve as a potential biomarker.
循环微RNA(miRNA)是多种疾病中的潜在生物标志物。然而,它们是否可作为人类成人暴发性心肌炎(FM)的生物标志物尚不清楚。通过微阵列分析检测循环miRNA表达谱,并通过定量实时PCR阵列进行验证。同时,利用京都基因与基因组百科全书(KEGG)通路分析来确定这些循环miRNA在FM中的关键作用。此外,对FM患者的miRNA与心功能参数进行相关性分析。最后,使用受试者工作特征曲线分析评估循环长链非编码RNA(lncRNA)表达在FM诊断中的敏感性和特异性。微阵列分析和定量实时PCR分析均显示,miR-47,63-3p和miR-4281在FM发病初期血浆中的表达上调,且随着临床症状恢复其水平也恢复正常。miR-47,63-3p和miR-4281的预测靶基因涉及多个途径,主要是炎症和心脏损伤反应。此外,miRNA富集与FM的严重程度呈负相关。另外,循环miR-47,63-3p在心肌梗死(MI)患者中的表达水平未发生变化,但对FM诊断具有较高的敏感性和特异性。本研究提供了FM患者循环miRNA的整体概况,其中miR-47,63-3p可作为一种潜在的生物标志物。