Background:Keloids are benign skin tumors characterized by fibroblast proliferation,tumor-like biological behavior,and excessive deposition of extracellular matrix in wounded skin.Ferroptosis,a type of programmed cell...Background:Keloids are benign skin tumors characterized by fibroblast proliferation,tumor-like biological behavior,and excessive deposition of extracellular matrix in wounded skin.Ferroptosis,a type of programmed cell death,is critical in tumor pathogenesis.We aimed to investigate the role of ferroptosis in keloid formation.Methods:We downloaded public high-throughput sequencing raw count data(GSE92566),containing three normal skin and four keloid samples,from the Gene Expression Omnibus database.Ferroptosis-related genes were obtained from the Ferroptosis database website.The ferroptosis-related differentially expressed genes(FRDEGs)were obtained by merging differentially expressed genes with ferroptosis-related genes.The FRDEGs were then used for Gene Ontology,Kyoto Encyclopedia of Genes and Genomes,Gene Set Enrichment Analysis,proteinprotein interaction(PPI)network,and microRNA(miRNA)-mRNA network analysis.Finally,real-time quantitative polymerase chain reaction(RT-qPCR)was performed to validate our findings.Results:We found 25 FRDEGs,including 8 up-regulated and 17 down-regulated genes.Pathway enrichment analysis revealed that the Hippo and transforming growth factorβsignaling pathways were significantly upregulated in keloids.In contrast,regulation of the peroxisome proliferator-activated receptor signaling pathway,glutathione metabolism,and unsaturated fatty acid metabolic process were down-regulated.PPI and FRDEGs hub networks were constructed using the STRING database and Cytoscape software.Ten hub genes were identified,including PLA2G6,RARRES2,SNCA,CYP4F8,CDKN2A,ALOX12,FABP4,ALOX12B,NEDD4,and NEDD4L.We constructed a miRNA-mRNA network,which predicted hsa-mir-155-5p,hsa-let-7b-5p,hsa-mir-124-3p,hsa-mir-145-5p,hsa-mir-328-3p,hsa-mir-24-3p,and hsa-mir-10b-5p as the most connected miRNAs regulating ferroptosis in keloids.Finally,we verified the expression levels of the hub genes by RT-qPCR,which confirmed that ALOX12,ALOX12B,and CYP4F8 expression were reduced in keloids.Conclusions:This study provides novel information on ferroptosis-mediated keloid pathogenesis,underscoring the importance of further research in this area to unlock new therapeutic avenues for keloid treatment.展开更多
基金the National Natural Science Foundation of China(grant no.81971846)National High Level Hospital Clinical Research Funding(grant no.2022-PUMCH-B-042).
文摘Background:Keloids are benign skin tumors characterized by fibroblast proliferation,tumor-like biological behavior,and excessive deposition of extracellular matrix in wounded skin.Ferroptosis,a type of programmed cell death,is critical in tumor pathogenesis.We aimed to investigate the role of ferroptosis in keloid formation.Methods:We downloaded public high-throughput sequencing raw count data(GSE92566),containing three normal skin and four keloid samples,from the Gene Expression Omnibus database.Ferroptosis-related genes were obtained from the Ferroptosis database website.The ferroptosis-related differentially expressed genes(FRDEGs)were obtained by merging differentially expressed genes with ferroptosis-related genes.The FRDEGs were then used for Gene Ontology,Kyoto Encyclopedia of Genes and Genomes,Gene Set Enrichment Analysis,proteinprotein interaction(PPI)network,and microRNA(miRNA)-mRNA network analysis.Finally,real-time quantitative polymerase chain reaction(RT-qPCR)was performed to validate our findings.Results:We found 25 FRDEGs,including 8 up-regulated and 17 down-regulated genes.Pathway enrichment analysis revealed that the Hippo and transforming growth factorβsignaling pathways were significantly upregulated in keloids.In contrast,regulation of the peroxisome proliferator-activated receptor signaling pathway,glutathione metabolism,and unsaturated fatty acid metabolic process were down-regulated.PPI and FRDEGs hub networks were constructed using the STRING database and Cytoscape software.Ten hub genes were identified,including PLA2G6,RARRES2,SNCA,CYP4F8,CDKN2A,ALOX12,FABP4,ALOX12B,NEDD4,and NEDD4L.We constructed a miRNA-mRNA network,which predicted hsa-mir-155-5p,hsa-let-7b-5p,hsa-mir-124-3p,hsa-mir-145-5p,hsa-mir-328-3p,hsa-mir-24-3p,and hsa-mir-10b-5p as the most connected miRNAs regulating ferroptosis in keloids.Finally,we verified the expression levels of the hub genes by RT-qPCR,which confirmed that ALOX12,ALOX12B,and CYP4F8 expression were reduced in keloids.Conclusions:This study provides novel information on ferroptosis-mediated keloid pathogenesis,underscoring the importance of further research in this area to unlock new therapeutic avenues for keloid treatment.
