Elucidating the interplay of ferroptosis-related genes in keloid formation:Insights from bioinformatics analysis  

作　　者：Zikai Qiu Mingzi Zhang Wenchao Zhang Loubin Si Nanze Yu Xiaojun Wang 

机构地区：[1]Department of Plastic and Reconstructive Surgery,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,100730,China

出　　处：《Chinese Journal of Plastic and Reconstructive Surgery》2024年第2期57-64,共8页

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).

摘　　要：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

关 键 词：KELOID Ferroptosis BIOINFORMATICS Fatty acid metabolic process 

分 类 号：R622[医药卫生—整形外科]