The hub genes and their potential regulatory mechanisms in chronic spontaneous urticaria revealed by integrated transcriptional expression analysis

Abstract

Chronic spontaneous urticaria (CSU) is a recurrent disease characterized by wheals and or angioedema, and its pathogenesis is still unclear. The microarray datasets of skin tissue from CSU patients and healthy controls were integrated and analysed in Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were identified using the NetworkAnalyst tool. Then, the Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Subsequently, a protein-protein interaction (PPI) network of DEGs was constructed by STRING and the related hub genes were identified through the MOCDE tool. The potential miRNAs targeting hub genes were predicted based on the intersection of three online databases, namely TargetScanHuman, TargetBase and miRNet. Differentially expressed lncRNAs (DElncRNAs) was performed using the GEO2R tool. The potential miRNAs targeting DElncRNAs were predicted through miRNet. Finally, the shared miRNAs targeting both hub genes and DElncRNAs were used to construct an mRNA/miRNA/lncRNA regulatory network. A total of 296 DEGs were obtained, which were mainly enriched in inflammatory and immune responses.Further, 14 hub genes were identified by the PPI network of DEGs. Clinical correlation analysis showed that the mRNA expressions of S100A7, S100A8, S100A9, S100A12, IL6 and SOCS3 in CSU were positively correlated with the 7-day urticaria activity score (UAS7), and their potential diagnostic value was supported by the receiver operating characteristic curve (ROC) analysis. Five up-regulated lncRNAs in the cytoplasm were obtained by DElncRNAs analysis. The ROC analysis showed that PVT1, SNHG3 and ZBTB20 − AS1 was of potential diagnostic value for CSU. Eight shared miRNAs targeting both hub genes and DElncRNAs were identified and used to construct a competing endogenous RNA (ceRNA) network. It was found that the IL-6/ miR − 149 − 5p/ZBTB20 − AS1 axis might play an important role in the activation of | 841 LIU et al.

Knockdown of miR-155 alleviates skin damage in rats with chronic spontaneous urticaria by modulating the JAK/STAT signaling pathway

“…Most CSUs fall into the category of IgE-mediated type I hypersensitivity diseases. The cells involved in type I hypersensitivity reactions mainly include a variety of inflammatory cells such as mast cells, basophils, lymphocytes, eosinophils and neutrophils [ 24 , 25 ]. Among them, mast cells are mainly located in the skin and submucosal layer.…”

Identification of key genes and molecular mechanisms of chronic urticaria based on bioinformatics

“…Bioinformatics is vital for analyzing genes in chronic urticaria. It manages and integrates diverse genetic and clinical data, detects variations associated with the condition, and elucidates disrupted pathways 17–19 . It studies gene expression, annotates functions, and constructs interaction networks to identify critical genes.…”

“…It manages and integrates diverse genetic and clinical data, detects variations associated with the condition, and elucidates disrupted pathways. 17 , 18 , 19 It studies gene expression, annotates functions, and constructs interaction networks to identify critical genes. Bioinformatics prioritizes relevant variants, compares genomes across populations, and employs machine learning for prediction.…”

Key genes and immune infiltration in chronic spontaneous urticaria: a study of bioinformatics and systems biology

“…As of now, two CSU studies have assessed skin gene expression ( 11 – 13 ), but joint analyses of these microarray datasets, GSE57178 and GSE72540 are limited. One recent study of these datasets recently reported that the IL-6/miR-149-5p/ZBTB20-AS1 axis may be involved in mast cell activation in CSU ( 14 ). The lesional immune cell infiltrate and core genes, however have not been investigated by bioinformatics analyses.…”