Abstract: BACKGROUND: Tibial transverse transport has emerged as a pivotal therapeutic approach for severe diabetic foot ulcers (Wagner grade III and above); however, its precise molecular regulatory mechanisms remain largely elusive.
OBJECTIVE: To establish an animal model of tibial transverse transport for diabetic foot ulcer treatment and perform transcriptome sequencing, aimed at identify significantly differentially expressed miRNAs and key target genes, as well as construct the corresponding miRNA-mRNA regulatory network.
METHODS: A diabetic foot ulcer wound model was established in rabbits and treated with tibial transverse transport. Peripheral blood samples were collected for miRNA-seq and mRNA-seq. Differentially expressed miRNAs and mRNAs were identified through bioinformatics analysis of sequencing data. Target genes of miRNAs were predicted using TargetScan and miRanda, and a miRNA-mRNA regulatory network was constructed. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and protein-protein interaction (PPI) analysis were performed on the target genes in the network. Core target genes were subsequently screened using the Maximal Clique Centrality and Degree algorithms.
RESULTS AND CONCLUSION: A total of 9 miRNAs and 2 667 mRNAs with significant differential expression were identified. Based on the differential analysis results and miRNA target gene predictions, a miRNA-mRNA regulatory network containing 7 miRNAs and 79 target genes was constructed. Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that these target genes were primarily involved in the metabolic pathway, protein processing in endoplasmic reticulum, FoxO signaling pathway, propanoate metabolism, N-glycan biosynthesis, and other signaling pathways. Protein-protein interaction analysis revealed the interaction between the expressed proteins of these target genes and identified BAG3, AKT3, PPP4C, SEC61A1, DNAJC3, USP7, DAD1, and SETD7 as the core target genes. This study identified a series of key miRNAs, target genes, and signaling pathways associated with the treatment of diabetic foot ulcers through transcriptome sequencing. These findings not only provide new candidate targets for treating diabetic foot ulcers but also open new avenues for further exploration of the therapeutic mechanisms of tibial transverse transport.

Key words: tibial transverse transport, diabetic foot ulcers, transcriptome sequencing, miRNA, miRNA-mRNA regulatory network