title: Regulatory mechanisms underlying sepsis progression in patients with tumor necrosis factor-α genetic variations.
abstract: 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,COPS2was found to be associated with transcriptional functions, whileFUSwas found to be involved in mRNA metabolic processes. Other DEGs, includingFBXW7andCUL3, were enriched in the ubiquitin-mediated proteolysis pathway. In addition, miR-15 was predicted to targetCOPS2andCUL3. The results of the present study suggested thatCOPS2,FUS,FBXW7andCUL3may be associated with sepsis in patients with TNF-α genetic variations. In the progression of sepsis,FBXW7andCUL3may participate in the ubiquitin-mediated proteolysis pathway, whereasCOPS2may regulate the phosphorylation and ubiquitination of the FUS protein. Furthermore,COPS2andCUL3may be novel targets of miR-15.
authors.affiliation: Emergency Trauma Department, Shanghai East Hospital, Shanghai 200120, P.R. China.
authors.forename: Yangzhou
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Emergency Trauma Department, Shanghai East Hospital, Shanghai 200120, P.R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: Han
authors.affiliation: Emergency Trauma Department, Shanghai East Hospital, Shanghai 200120, P.R. China.
authors.forename: Qinchuan
authors.initials: Q
authors.lastname: Li
authors.affiliation: Emergency Trauma Department, Shanghai East Hospital, Shanghai 200120, P.R. China.
authors.forename: Zengchun
authors.initials: Z
authors.lastname: Li
keywords: microRNA; microarray data; sepsis; tumor necrosis factor-α variation; ubiquitination