가와사키병 환아에서의 miRNA-200c와 miRNA-371-5p의 혈청 농도 증가
Elevated serum level of miRNA-200c and miRNA-371-5p in children with Kawasaki disease
Abstract
b>Background:/b> Kawasaki disease (KD) is a most common vasculitis in childhood, but its pathogenesis is not clearly understood and confirmatory diagnostic laboratories have not been established. MicroRNAs (miRNAs) are small, non-coding RNAs that regulate the expression of protein-coding genes and have been implicated in various biological processes. Recently, miRNA levels have been used as a novel non-invasive biomarker for diagnosis of various diseases. But, the relationship between circulating miRNAs and KD has not been reported previously. b>Methods:/b> Serum specimens were collected from children with KD (n=12) and healthy controls (n=6). We analyzed a total of 18 biologically independent serum samples rather than pooled serum. miRNA microarray assays were performed using the PANArray™ miRNA expression profiling kit ( PANAGENE Co., Daejeon, Korea). We used TargetScan and the DAVID program to obtain a list of enriched biological pathways in conserving genes targeted by miRNAs differentially expressed in KD patients. b>Results:/b> Among 158 miRNAs on the microarray DNA chip, a total of 19 were identified as significantly expressed in serum samples. miR-200c and miR-371-5p were significantly up-regulated in the KD group compared to the control group (i>P/i>=0.032, in both). By using TargetScan, we obtained a list of 421 and 542 genes predicted to be targeted by miR-200c and miR-371, respectively, and these genes were significantly (i>P/i>0.05) clustered in 17 and 3 pathways, respectively. Many of them are major pathways involved in inflammatory responses. b>Conclusions:/b> We identified elevated serum levels of miR-200c and miR-371-5p in children with KD. The present data support the hypothesis that the inflammatory response is a crucial mechanism for pathogenesis of KD, and miRNAs might be main regulators of this inflammatory response. To our knowledge, this is the first study to identify a specific miRNA profile and to elucidate the clinical significance of miRNA variations in KD.