Molecular Genetics & Genomic Medicine · 2019 · 12 citations · 30 references
Life SciencesCardiologyImmunologyGene ExpressionInflammationInnate ImmunityBiomarker DiscoveryCoronary Artery DiseaseEndothelial ActivationInflammatory BiomarkersMicrorna BiologyNeutrophil BiologyBiomarkersCoronary Lesion AssessmentEndothelial MigrationHuman Cell-based In Vitro ModelsLeukocyte Transendothelial MigrationMicroarray AnalysisMicrorna BiomarkersNeutrophil Involvement
BACKGROUND: Kawasaki disease (KD) patients could develop coronary artery lesion (CAL) which threatens children's life. A previous study identified KD biomarker miRNAs that could discriminate KD patients from febrile non-KD patients. We wonder whether these KD prediction biomarkers could be further applied to predict CAL formation in KD patients. METHODS: To examine this hypothesis, we conducted a meta-analysis, miRNA mimic transfection, in vitro cell model and microarray assays. RESULTS: We first showed that miR-182-5p and miR-183-5p kept higher levels in the KD patients with CAL than those without CAL (p < .05). Further machine learning alignment confirmed that CAL formation could be predicted, with an auROC value of 0.86. We further treated neutrophil cells with miR-182-5p mimic, followed by in vitro transendotherial migration assay. As a result, miR-182-5p overexpression significantly (p < .05) enhanced neutrophil cells to infiltrate the endothelial layer composed of human coronary artery endothelium cells. Further microarray assay and pathway enrichment analysis showed that the genes activated with miR-182-5p overexpression were significantly enriched in the leukocyte transendothelial migration pathway (kegg_pathway_194, p < .05). CONCLUSION: Therefore, our study suggested that miR-182-5p enhanced in vitro leukocyte infiltration by activating the leukocyte transendothelial migration pathway in CAL formation in KD.
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