Identification of hub genes and pathways associated with cellular senescence in diabetic foot ulcers via comprehensive transcriptome analysis.

ABSTRACT

This research aimed to find important genes and pathways related to cellular senescence (CS) in diabetic foot ulcers (DFU) and to estimate the possible pathways through which CS affects diabetic foot healing. The GSE80178 dataset was acquired from the Gene Expression Omnibus (GEO) database, containing six DFU and three diabetic foot skin (DFS) samples. The limma package was used to identify differentially expressed genes (DEGs). At the same time, DEGs associated with CS (CS-DEGs) were found using the CellAge database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted on the CS-DEGs. A protein-protein interaction (PPI) network was built using the String database, and the cytoHubba plug-in within Cytoscape helped identify hub genes. Lastly, the miRNA-TF-mRNA regulatory network for these hub genes was established. In total, 66 CS-DEGs were obtained. These genes mainly focus on CS, Kaposi sarcoma-associated herpesvirus infection and Toll-like receptor signalling pathway. Eight hub genes were identified to regulate cell senescence in DFU, including TP53, SRC, SIRT1, CCND1, EZH2, CXCL8, AR and CDK4. According to miRNA-TF-mRNA regulatory network, hsa-mir-132-3p/SIRT1/EZH2 axis is involved in senescence cell accumulation in DFU.