Identification of a functional circRNA-miRNA-mRNA regulatory network in infantile hemangioma by bioinformatics analysis

Several circRNA have been reported to serve critical roles in various biological processes of human body. The present study aimed to build a circRNA-based competing endogenous RNA (ceRNA) network and explore the regulatory mechanisms of circRNA in infantile hemangiomas (IH). Differentially expressed circRNA, miRNA, and mRNA were downloaded from the gene expression synthesis (GEO) microarray database (GSE98795, GSE69136, and GSE127487). Cancer-specific circRNA database (CSCD), miRDB and Targetscan were employed to predict the targets of RNA. A total of 855 DEcircRNAs, 69 differentially expressed miRNAs (DEmiRNAs), and 3233 differentially expressed mRNAs (DEmRNAs) appeared as genes that were aberrantly expressed in IH. The circRNA-miRNA-mRNA network was constructed based on 108 circRNAs, 7 miRNAs, 274 mRNAs in IH. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis indicated hypoxia-inducible factors (HIF)-1 signaling pathway and Notch signaling pathway were significantly enriched in IH with being constructed a ceRNA regulatory network. Furthermore, protein-protein interaction (PPI) network and Cytoscape showed the top 10 hub genes that regulate angiogenesis, namely FBXW7, CBLB, HECW2, FBXO32, FBXL7, KLHL5, EP300, MAPK1, MEF2C, and PLCG1. Our findings provide a deeper understanding the circRNA-related ceRNA regulatory mechanism in IH. This study further perfected the circRNA-miRNA-mRNA regulatory network related to IH and explored the potential function of mRNA in this network. It provides more understanding for the circRNA-related ceRNA regulation mechanism in the pathogenesis of IH.