Regulatory mechanisms underlying sepsis progression in patients with tumor necrosis factor-α genetic variations.

The present study aimed to investigate the regulatory mechanisms underlying sepsis progression in patients with tumor necrosis factor (TNF)-α genetic variations. The GSE5760 expression profile data, which was downloaded from the Gene Expression Omnibus database, contained 30 wild-type (WT) and 28 mutation (MUT) samples. Differentially expressed genes (DEGs) between the two types of samples were identified using the Student's t-test, and the corresponding microRNAs (miRNAs) were screened using WebGestalt software. An integrated miRNA-DEG network was constructed using the Cytoscape software, based on the interactions between the DEGs, as identified using the Search Tool for the Retrieval of Interacting Genes/Proteins database, and the correlation between miRNAs and their target genes. Furthermore, Gene Ontology and pathway enrichment analyses were conducted for the DEGs using the Database for Annotation, Visualization and Integrated Discovery and the KEGG Orthology Based Annotation System, respectively. A total of 390 DEGS between the WT and MUT samples, along with 11 -associated miRNAs, were identified. The integrated miRNA-DEG network consisted of 38 DEGs and 11 miRNAs. Within this network, was found to be associated with transcriptional functions, while was found to be involved in mRNA metabolic processes. Other DEGs, including and , were enriched in the ubiquitin-mediated proteolysis pathway. In addition, miR-15 was predicted to target and . The results of the present study suggested that , , and may be associated with sepsis in patients with TNF-α genetic variations. In the progression of sepsis, and may participate in the ubiquitin-mediated proteolysis pathway, whereas may regulate the phosphorylation and ubiquitination of the FUS protein. Furthermore, and may be novel targets of miR-15.