Cross talk between bacterial and human gene networks enriched using ncRNAs in IBD disease

Abstract

Inflammatory bowel disease (IBD) is a long-term inflammatory immune-mediated gut illness with several extra-intestinal complications. The aims of this study were to identify a novel network-based meta-analysis approach on the basis of the combinations of the differentially expressed genes (DEGs) from microarray data, to enrich the functional modules from human protein–protein interaction (PPI) and gene ontology (GO) data, and to profile the ncRNAs on the genes involved in IBD. The gene expression profiles of GSE126124, GSE87473, GSE75214, and GSE95095 are obtained from the Gene Expression Omnibus (GEO) database based on the study criteria between 2017 and 2022. The DEGs were screened by the R software. DEGs were then used to examine gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The ncRNAs including the miRNAs and ceRNAs were predicted on the PPIs visualized using Cytoscape. Enrichment analysis of genes with differential expression (n = 342) using KEGG and GO showed that the signaling pathways related with staphylococcus aureus and pertussis bacterial infections may stimulate the immune system and exacerbate IBD via the interaction with human proteins including Fibrinogen gamma chain (FGG), Keratin 10 (KRT10), and Toll like receptor 4 (TLR4). By building a ceRNA network, lncRNA XIST and NEAT1 were determined by affecting common miRNAs, hsa-miR-6875-5p, hsa-miR-1908-5p, hsa-miR-186-5p, hsa-miR-6763-5p, hsa-miR-4436a, and hsa-miR-520a-5p. Additionally, the chromosome regions including NM_001039703 and NM_006267, which produce the most potent circRNAs play a significant role in the ceRNA network of IBD. Also, we predicted the siRNAs that would be most effective against the bacterial genes in staphylococcus aureus and pertussis infections. These findings suggested that three genes (FGG, KRT10, and TLR4), six miRNAs (hsa-miR-6875-5p, hsa-miR-1908-5p, hsa-miR-186-5p, hsa-miR-4436a, hsa-miR-520a-5p, and hsa-miR-6763-5p), two lncRNAs (XIST and NEAT1), and chromosomal regions including NM_001039703 and NM_006267 with the production of the most effective circRNAs are involved in the ncRNA-associated ceRNA network of IBD. These ncRNA profiles are related to the described gene functions and may play therapeutic targets in controlling inflammatory bowel disease.