Underlying Genes and Molecular Mechanism of Keloids Investigated by Integrated Bioinformatics Analysis
Abstract Background: We aimed to identify the overlapping differentially expressed genes (DEGs) of keloids distinguished from normal scar and normal skin and relevant underlying mechanism using integrated bioinformatics methods.Methods: The expression profiles of 18 keloid samples, 7 normal skin and 5 normal scar, were obtained from the GSE7890, GSE44270, GSE92566, and GSE3189 datasets in the Gene Expression Omnibus database. DEGs were identified using the LIMMA package in R. Gene ontology (GO) functional enrichment analysis was performed using the R software. A DEG-associated protein–protein interaction (PPI) network was constructed using STRING and MCODE was used for module analysis of the PPI network. Moreover, the hub genes were verified by qRT-PCR. The predicted DEGs, their regulatory miRNA and TF regulation network was analyzed using miRnet. Results: A total of 978 common DEGs were identified in the keloid samples. Genes with more than 45 interaction degrees, including neuropeptide Y (NPY), opioid receptor mu 1 (OPRM1), cholinergic receptor muscarinic 2 (CHRM2), and proopiomelanocortin (POMC), were found in the PPI network. Hsa-miR-335 and Sp1 as upstream-regulators regulated CHRM2, NPY, and POMC. Functional enrichment analysis revealed that hub genes were commonly enriched in the “G protein-coupled receptor signaling pathway” GO_BP termConclusion: Taken together, CHRM2, NPY, POMC, and OPRM1 potentially have crucial roles in keloid disease. Furthermore, miR-335 and Sp1 are potential targets for preventing keloid formation.