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Circulating miR-4763-3p is a novel potential biomarker candidate for human adult fulminant myocarditis

ABSTRACT: Circulating miRNA expression profiles were detected by microarray analysis.qPCR arrays were performed to validate the potential miRNAs.KEGG pathway analysis was used to determine the critical roles of these circulating miRNAs in FM. Correlation analysis was employed between miRNAs and the parameters of cardiac functions in FM. The sensitivity and specificity of circulating lncRNA expression in FM diagnosis were evaluated using receiver operating characteristic curve analysis. Microarray and qPCR analysis showed that the expression of miR-4763-3p and miR-4281 were up-regulated 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 was unchanged in MI and patients and miR-4281 showed high sensitivity and specificity for FM diagnosis.This study provides global profile of circulating miRNAs in patients with FM, among which miR-4763-3p and miR-4281 could serve as potential biomarkers.

ORGANISM(S): Homo sapiens

PROVIDER: GSE148153 | GEO | 2020/04/07

REPOSITORIES: GEO

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Project description:Rationale: Currently, there are no blood-based biomarkers with clinical utility for acute ischemic stroke (IS). microRNAs (miRNAs) show promise as disease markers due to their cell-type specific expression patterns and stability in peripheral blood. Objective: To identify circulating miRNAs associated with acute IS, determine their temporal course up to 90 days post-stroke, and explore their utility as an early diagnostic marker. Methods and Results: We used RNA sequencing to study expression changes of circulating miRNAs in a discovery sample of 20 IS patients and 20 matched healthy control subjects (HCs). We further applied qRT-PCR in independent samples for validation (40 IS patients and 40 matched controls), replication (200 IS patients, 100 HCs), and in 72 patients with transient ischemic attacks (TIA). Sampling of patient plasma was done immediately upon hospital arrival. We identified, validated, and replicated three differentially expressed miRNAs, which were upregulated in IS patients compared to both HCs (miR-125a-5p [1.8-fold; P=1.5x10-6], miR-125b-5p [2.5-fold; P=5.6x10-6], and miR-143-3p [4.8-fold; P=7.8x10-9]) and TIA patients (miR-125a-5p: P=0.003, miR-125b-5p: P=0.003, miR-143-3p: P=0.005). Longitudinal analysis of expression levels up to 90 days after stroke revealed a normalization to control levels for miR-125b-5p and miR-143-3p starting at day two, while miR-125a-5p remained elevated. Levels of all three miRNAs depended on platelet numbers in a platelet spike-in experiment, but were unaffected by chemical hypoxia in N2a cells and in experimental stroke models. In a random forest classification, miR-125a-5p, miR-125b-5p and miR-143-3p differentiated between HCs and IS patients with an area under the curve (AUC) of 0.90 (sensitivity: 85.6%; specificity: 76.3%), which was superior to multimodal cranial computed tomography obtained for routine diagnostics (sensitivity: 72.5%) and previously reported biomarkers of acute IS (neuron specific enolase: AUC=0.69, interleukin 6: AUC=0.82). Conclusions: A set of circulating miRNAs (miR-125a-5p, miR-125b-5p, miR-143-3p) associates with acute IS and might have clinical utility as an early diagnostic marker.

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Circulating miR-4763-3p is a novel potential biomarker candidate for human adult fulminant myocarditis

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