Serum exosomal microRNA let‐7i‐3p as candidate diagnostic biomarker for Kawasaki disease patients with coronary artery aneurysm

Abstract

Kawasaki disease (KD) is a systemic vasculitis syndrome that leads to coronary artery aneurysm (CAA). While echocardiography is the most important imaging modality for coronary artery assessment, a specific diagnostic biomarker complementary for CAA has not been reported. We aimed to analyze the profiles of exosomal miRNAs extracted from the serum of KD patients and controls to identify candidate biomarkers for CAA. Serum samples from 39 healthy children, 42 CAA patients, 38 coronary artery dilatation (CAD) patients and 45 virus‐infected patients including 24 EBV patients and 21 ADV patients were randomly selected. Next generation sequencing was used to analyze serum exosomal miRNA to detect differentially expressed miRNAs. Biomarker candidates were validated by qRT‐PCR. One hundred (and) ninety‐six differentially expressed miRNAs (DEMs) were detected in CAA patients and healthy children. There were 70 DEMs and 140 DEMs in CAA patients versus CAD patients, and in CAA patients versus virus‐infected patients, respectively. We selected the three most upregulated (let‐7i‐3p, miR‐17‐3p, and miR‐210‐5p) and the three most downregulated miRNAs (miR‐6743‐5p, miR‐1246, and miR‐6834‐5p) in the DEMs, which were expressed differentially in CAA patients versus healthy children, and in CAA patients versus virus‐infected patients, not in virus‐infected patients versus healthy children, as biomarker candidates. Excluded DEMs of CAD and virus‐infected patients, let‐7i‐3p was detected by sequence data analysis as a biomarker candidate for CAA patients, and then validated by qRT‐PCR in a larger set of clinical samples. As a biomarker candidate, let‐7i‐3p provides an additional means of diagnosing CAA patients. Additionally, miRNA biomarkers complement ultrasonic imaging, allowing for greater diagnostic precision. © 2019 IUBMB Life, 2019

Association study of miR‐149, miR‐196a2, and miR‐499a polymorphisms with coronary artery aneurysm of Kawasaki disease in southern Chinese population

“…Recent studies by our team have shown that reduced platelet‐derived miR‐223 leads to severe coronary pathology, which promotes vascular smooth muscle cell differentiation and reduces the occurrence of KD complicated with CAA 28 and serum exosomal miR‐Let‐7i‐3p as a new potential biomarker for the diagnosis of KD patients with CAA. 29 KD is an acute systemic vasculitis of unknown etiology that usually affects infants and young children aged under 5 years. 3 Children with severe disease will be complicated by CAAs, leading to a series of cardiovascular sequelae.…”

miRNAs and isomiRs: Serum-Based Biomarkers for the Development of Intellectual Disability and Autism Spectrum Disorder in Tuberous Sclerosis Complex

“…Our results demonstrated the relevant role of miRNAs (hsa-let-7i-3p and hsa-miR-409-5p) in the prediction of the early development of ASD or ID alone in TSC patients (AUC 0.894 and 0.880, respectively). Several studies have investigated the role of hsa-let-7i-3p in multiple diseases outside the brain [ 65 , 66 , 67 , 68 ]. On the other hand, the association between hsa-miR-409-5p and neuropsychiatric diseases, such as depression, has been reported in multiple research studies in rodents [ 69 ].…”

Distinguishing Kawasaki Disease from Febrile Infectious Disease Using Gene Pair Signatures

“…A recent study found that the methylation level of the HAMP promoter significantly decreases in KD, and this hypomethylation feature can serve as biomarkers for KD diagnosis [10]. Our previous studies found that serum exosomal microRNAs could serve as candidate biomarkers in KD [11] and identified microRNAs that are closely related to coronary aneurysms in KD patients [12]. Although methylation and miRNA are sufficiently specific as KD-related diagnostic biomarkers, they may have limited power due to the small sample size of these studies.…”