In silico analysis of the molecular regulatory networks in peripheral arterial occlusive disease

Peripheral arterial occlusive disease (PAOD) is a global public health concern that decreases the quality of life of the patients and can lead to disabilities and death. The aim of this study was to identify the genes and pathways associated with PAOD pathogenesis, and the potential therapeutic targets.

Differentially expressed genes (DEGs) and miRNAs related to PAOD were extracted from the GSE57691 dataset and through text mining. Additionally, bioinformatics analysis was applied to explore gene ontology, pathways and protein-protein interaction of those DEGs. The potential miRNAs targeting the DEGs and the transcription factors (TFs) regulating miRNAs were predicted by multiple different databases.

A total of 59 DEGs were identified, which were significantly enriched in the inflammatory response, immune response, chemokine-mediated signaling pathway and JAK-STAT signaling pathway. Thirteen genes including IL6, CXCL12, IL1B, and STAT3 were hub genes in protein-protein interaction network. In addition, 513 miRNA-target gene pairs were identified, of which CXCL12 and PTPN11 were the potential targets of miRNA-143, and IL1B of miRNA-21. STAT3 was differentially expressed and regulated 27 potential target miRNAs including miRNA-143 and miRNA-21 in TF-miRNA regulatory network.

In summary, inflammation, immune response and STAT3-mediated miRNA-target genes axis play an important role in PAOD development and progression.