Abstract
Kawasaki disease (KD) causes acute systemic vasculitis and has unknown etiology. Since the acute stage of KD is the most relevant, the aim of the present study was to identify hub genes in acute KD by bioinformatics analysis. We also aimed at constructing microRNA (miRNA)–messenger RNA (mRNA) regulatory networks associated with acute KD based on previously identified differentially expressed miRNAs (DE-miRNAs). DE-mRNAs in acute KD patients were screened using the mRNA expression profile data of GSE18606 from the Gene Expression Omnibus. The functional and pathway enrichment analysis of DE-mRNAs were performed with the DAVID database. Target genes of DE-miRNAs were predicted using the miRWalk database and their intersection with DE-mRNAs was obtained. From a protein–protein interaction (PPI) network established by the STRING database, Cytoscape software identified hub genes with the two topological analysis methods maximal clique centrality and Degree algorithm to construct a miRNA-hub gene network. A total of 1,063 DE-mRNAs were identified between acute KD and healthy individuals, 472 upregulated and 591 downregulated. The constructed PPI network with these DE-mRNAs identified 38 hub genes mostly enriched in pathways related to systemic lupus erythematosus, alcoholism, viral carcinogenesis, osteoclast differentiation, adipocytokine signaling pathway and tumor necrosis factor signaling pathway. Target genes were predicted for the up-regulated and down-regulated DE-miRNAs, 10,203, and 5,310, respectively. Subsequently, 355, and 130 overlapping target DE-mRNAs were obtained for upregulated and downregulated DE-miRNAs, respectively. PPI networks with these target DE-mRNAs produced 15 hub genes, six down-regulated and nine upregulated hub genes. Among these, ten genes (ATM, MDC1, CD59, CD177, TRPM2, FCAR, TSPAN14, LILRB2, SIRPA, and STAT3) were identified as hub genes in the PPI network of DE-mRNAs. Finally, we constructed the regulatory network of DE-miRNAs and hub genes, which suggested potential modulation of most hub genes by hsa-miR-4443 and hsa-miR-6510-5p. SP1 was predicted to potentially regulate most of DE-miRNAs. In conclusion, several hub genes are associated with acute KD. An miRNA–mRNA regulatory network potentially relevant for acute KD pathogenesis provides new insights into the underlying molecular mechanisms of acute KD. The latter may contribute to the diagnosis and treatment of acute KD.
Highlights
Kawasaki disease (KD) is responsible for acute systemic vasculitis and it is a high-risk factor of acquired heart disease in children (Gordon et al, 2009)
Gene ontology (GO) biological process (BP) analysis showed that these 1,063 DEmRNAs were significantly enriched in various roles (Figure 2A)
Microarray technology coupled with bioinformatics tools has been used to identify the novel genes associated with the pathogenesis, diagnosis and treatment of KD (Wu et al, 2019; Yazdan et al, 2020)
Summary
Kawasaki disease (KD) is responsible for acute systemic vasculitis and it is a high-risk factor of acquired heart disease in children (Gordon et al, 2009). Diagnosis of KD still relies on presentation of clinical symptoms, such as persistent fever of more than 5 days, conjunctival nonsuppurative hyperemia, red bayberry tongue, rash, lymph node enlargement, fingertip swelling, annular peeling, and systemic vascular inflammatory lesions (McCrindle et al, 2017). The etiology of KD remains unknown, the role of alteration of genes and their regulation has become increasingly relevant. The latter is based on the reported presence of susceptibility genes and single nucleotide polymorphisms (Onouchi, 2018; Kumrah et al, 2020) specific signaling pathways (Bijnens et al, 2018; Lv et al, 2019) and genetic predisposition (Uehara et al, 2003). Diagnosis and treatment of KD will benefit from a comprehensive understanding of the disease at the molecular level
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
