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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, COPS2 was found to be associated with transcriptional functions, while FUS was found to be involved in mRNA metabolic processes. Other DEGs, including FBXW7 and CUL3, were enriched in the ubiquitin-mediated proteolysis pathway. In addition, miR-15 was predicted to target COPS2 and CUL3. The results of the present study suggested that COPS2, FUS, FBXW7 and CUL3 may be associated with sepsis in patients with TNF-α genetic variations. In the progression of sepsis, FBXW7 and CUL3 may participate in the ubiquitin-mediated proteolysis pathway, whereas COPS2 may regulate the phosphorylation and ubiquitination of the FUS protein. Furthermore, COPS2 and CUL3 may be novel targets of miR.15. [ABSTRACT FROM AUTHOR]

Background: The study aimed to investigate the expression changes of genes in colorectal cancer (CRC) and screen the potential molecular targets. Methods: The GSE37178 of mRNA expression profile including the CRC samples extracted by surgical resection and the paired normal samples was downloaded from Gene Expression Omnibus database. The genes whose expressions were changed at four different time points were screened and clustered using Mfuzz package. Then DAVID was used to perform the functional and pathway enrichment analysis for genes in different clusters. The protein-protein interaction (PPI) networks were constructed for genes in the clusters according to the STRING database. Furthermore, the related-transcription factors (TFs) and microRNAs (miRNAs) were obtained based on the resources in databases and then were combined with the PPI networks in each cluster to construct the integrated network containing genes, TFs and miRNAs. Results: As a result, 314 genes were clustered into four groups. Genes in cluster 1 and cluster 2 showed a decreasing trend, while genes in cluster 3 and cluster 4 presented an increasing trend. Then 18 TFs (e.g., TCF4, MEF2C and FOS) and 18 miRNAs (e.g., miR-382, miR-217, miR-1184, miR-326 and miR-330-5p) were identified and three integrated networks for cluster 1, 3, and 4 were constructed. Conclusions: The results implied that expression of PITX2, VSNL1, TCF4, MEF2C and FOS are time-related and associated with CRC development, accompanied by several miRNAs including miR-382, miR-217, miR-21, miR-1184, miR- 326 and miR-330-5p. All of them might be used as potential diagnostic or therapeutic target molecules for CRC. [ABSTRACT FROM AUTHOR]