Yun Ki Wook, Lee Ji Young, Yun Sin Weon, Lim In Seok, Choi Eung Sang
Department of Pediatrics, Chung-Ang University Hospital, 224-1 Heukseok-dong, Dongjak-gu, Seoul, 156-755, Korea.
Pediatr Cardiol. 2014 Jun;35(5):745-52. doi: 10.1007/s00246-013-0846-6. Epub 2013 Nov 21.
MicroRNAs (miRNAs) are small, non-coding RNAs that regulate the expression of protein-coding genes. Recently, miRNA levels have been used as a novel non-invasive biomarker for the diagnosis of various diseases. We aimed to identify serum miRNAs elevated in patients with Kawasaki disease (KD) and to explore the potential biological function of identified candidate miRNAs. Serum specimens were collected from children with KD (n = 12) and healthy controls (n = 6). miRNA microarray assays were performed using the PANArray™ miRNA expression profiling kit (PANAGENE Co., Daejeon, Korea). We used TargetScan and the database for annotation, visualization, and integrated discovery program to obtain a list of enriched biological pathways targeted by miRNAs elevated in KD patients. As a result, miR-200c and miR-371-5p were significantly upregulated in the KD group compared with the control group (p = 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 (p < 0.05) clustered in 17 and 3 pathways, respectively. Many of them are major pathways involved in inflammatory responses. The present data support the hypothesis that the inflammatory response is a crucial mechanism for pathogenesis of KD, and miRNAs might be the main regulators of this inflammatory response.
微小RNA(miRNA)是一类小的非编码RNA,可调节蛋白质编码基因的表达。最近,miRNA水平已被用作诊断各种疾病的新型非侵入性生物标志物。我们旨在鉴定川崎病(KD)患者血清中升高的miRNA,并探讨所鉴定的候选miRNA的潜在生物学功能。从KD患儿(n = 12)和健康对照(n = 6)中收集血清标本。使用PANArray™ miRNA表达谱分析试剂盒(韩国大田PANAGENE公司)进行miRNA微阵列分析。我们使用TargetScan以及注释、可视化和综合发现程序数据库,以获得KD患者中升高的miRNA所靶向的富集生物途径列表。结果,与对照组相比,KD组中miR-200c和miR-371-5p显著上调(两者p = 0.032)。通过使用TargetScan,我们分别获得了预计被miR-200c和miR-371靶向的421个和542个基因列表,这些基因分别在17条和3条途径中显著聚类(p < 0.05)。其中许多是参与炎症反应的主要途径。目前的数据支持炎症反应是KD发病机制的关键机制这一假设,并且miRNA可能是这种炎症反应的主要调节因子。