Gene expression profiles in keloids have also been determined and have identified some important differentially expressed genes (DEGs). Several studies have focused on genetic factors in the pathogenesis of keloid formation however, no single genetic cause has been identified. Īccumulating evidence indicates a genetic predisposition for keloid because its incidence is greater in twins, families, and Asian and African ethnicities. Keloids are unaesthetic and often accompanied by a psychological burden that results in decreased quality of life. The growth of keloid can last for months to years and often causes pain, itching, and even movement restrictions. Different from normal scar, keloid possesses tumor analogous properties including invasive uncontrolled growth and frequent relapses. Keloid is a morbid and unique fibro-proliferative dermal disorder formed by an abnormal scarring response to injury. GNG13, ADCY8, NPY and HTR1A may act as core genes in keloid formation and these core genes establish relationship with SP1 and miRNA (hsa-mir-372, hsa-mir-20, hsa-mir-10b), which may influence multiple signaling pathways in the pathogenesis of keloid. Furthermore, the expression of core regulatory genes ( GNG13, ADCY8, HTR1A and NPY) was validated in clinical samples. In the TF/miRNA-target gene network, both hsa-mir-372 and hsa-mir-20 had a regulatory effect on GNG13, ADCY8 was predicted to be target by hsa-mir-10b, and HTR1A and NPY were potentially by SP1. Furthermore, nine core miRNAs (hsa-mir-124, hsa-let-7, hsa-mir-155, hsa-mir-26a, hsa-mir-941, hsa-mir-10b, hsa-mir-20, hsa-mir-31 and hsa-mir-372), and two core TFs (SP1 and TERT) were identified to play important roles in keloid formation. Seven core genes all belong to MCODE1 and were enriched in the “G protein coupled receptor signaling pathway” of the GO biological process category. We identified 628 DEGs, of which 626 were up-regulated and 2 were down-regulated. Core regulatory genes were verified by RT-qPCR. Regulatory relationships between TF/miRNA and target genes were predicted with miRnet and cytoscape. DEG-associated protein–protein interaction (PPI) network was constructed by STRING, followed by module selection from the PPI network based on the MCODE analysis. Gene Ontology (GO) functional enrichment analysis was also performed with R software. Differentially expressed genes (DEGs) were identified between keloid and normal skin samples as well as keloid and normal scar samples with R Project for Statistical Computing. Gene expression profiles (GSE7890, GSE92566, GSE44270 and GSE3189) of 5 normal scar samples, 10 normal skin samples and 18 keloid samples from the Gene Expression Omnibus (GEO) database were interrogated. Here, we investigated the regulatory genes, micro-RNAs (miRNAs) and transcription factors (TFs) that influence keloid development by comparing keloid and normal scar as well as keloid and normal skin. The mechanism of keloid formation has not been fully elucidated, especially during abnormal scarring. Keloid is a benign fibro-proliferative dermal tumor formed by an abnormal scarring response to injury and characterized by excessive collagen accumulation and invasive growth.
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