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pmid:36118873

Identifying hub genes and miRNAs in Crohn's disease by bioinformatics analysis.

Yuxin Sun · Daxing Cai · Weitao Hu · Taiyong Fang

Frontiers in genetics · 2022 doi:10.3389/fgene.2022.950136

Paper

complete

Experiment

partial

Data

partial

Analysis

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Identifying hub genes and miRNAs in Crohn's disease by bioinformatics analysis.
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10.3389/fgene.2022.950136
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Yuxin Sun
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Daxing Cai
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Weitao Hu
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Taiyong Fang
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Frontiers in genetics
year
2022
abstract
Introduction: Crohn's disease (CD) is a disease that manifests mainly as chronic inflammation of the gastrointestinal tract, which is still not well understood in terms of its pathogenesis. The aim of this study was to use bioinformatics analysis to identify differentially expressed genes (DEGs) and miRNAs with diagnostic and therapeutic potential in CD. Materials and methods: Three CD datasets (GSE179285, GSE102133, GSE75214) were downloaded from the Gene Expression Omnibus (GEO) database. DEGs between normal and CD tissues were identified using the GEO2R online tool. The Gene Ontology (GO) term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the DEGs were conducted using the clusterProfiler function in the R package. Protein-protein interaction network (PPI) analysis and visualization were performed with STRING and Cytoscape. Ten hub genes were identified using cytoHubba's MCC algorithm and validated with datasets GSE6731 and GSE52746. Finally, the miRNA gene regulatory network was constructed by Cytoscape and NetworkAnalyst to predict potential microRNAs (miRNAs) associated with DEGs. Results: A total of 97 DEGs were identified, consisting of 88 downregulated genes and 9 upregulated genes. The enriched functions and pathways of the DEGs include immune system process, response to stress, response to cytokine and extracellular region. KEGG pathway analysis indicates that the genes were significantly enriched in Cytokine-cytokine receptor interaction, IL-17 signaling pathway, Rheumatoid arthritis and TNF signaling pathway. In combination with the results of the protein-protein interaction (PPI) network and CytoHubba, 10 hub genes including IL1B, CXCL8, CXCL10, CXCL1, CXCL2, CXCL5, ICAM1, IL1RN, TIMP1 and MMP3 were selected. Based on the DEG-miRNAs network construction, 5 miRNAs including hsa-mir-21-5p, hsa-mir-93-5p, hsa-mir-98-5p, hsa-mir-1-3p and hsa-mir-335-5p were identified as potential critical miRNAs. Conclusion: In conclusion, a total of 97 DEGs, 10 hub genes and 5 miRNAs that may be involved in the progression or occurrence of CD were identified in this study, which could be regarded as biomarkers of CD.
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Identification of DEGs between CD and normal samples was performed using GEO2R (http://www.ncbi.nlm.nih.gov/geo/geo2r). Adjusted p-values (adj. P) and Benjamini and Hochberg’s false discovery rates were applied to provide a balance between discovering statistically significant genes and limiting false positives. Probe sets without corresponding gene symbols or genes with more than one probe set were deleted or normalized, respectively. |Log FC (fold change)| >1 and adj. p-value <0.01 were considered statistically significant.
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Identification of DEGs between CD and normal samples was performed using GEO2R (http://www.ncbi.nlm.nih.gov/geo/geo2r).
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Probe sets without corresponding gene symbols or genes with more than one probe set were deleted or normalized, respectively. |Log FC (fold change)| >1 and adj. p-value <0.01 were considered statistically significant.
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The aim of this study was to use bioinformatics analysis to identify differentially expressed genes (DEGs) and miRNAs with diagnostic and therapeutic potential in CD. Materials and methods: Three CD datasets (GSE179285, GSE102133, GSE75214) were downloaded from the Gene Expression Omnibus (GEO) database. DEGs between normal and CD tissues were identified using the GEO2R online tool. The Gene Ontology (GO) term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the DEGs were conducted using the clusterProfiler function in the R package. Protein-protein interaction network (PPI) analysis and visualization were performed with STRING and Cytoscape. Ten hub genes were identified using cytoHubba's MCC algorithm and validated with datasets GSE6731 and GSE52746. Finally, the miRNA gene regulatory network was constructed by Cytoscape and NetworkAnalyst to predict potential microRNAs (miRNAs) associated with DEGs. Results: A total of 97 DEGs were identified, consisting of 88 downregulated genes and 9 upregulated genes. The enriched functions and pathways of the DEGs include immune system process, response to stress, response to cytokine and extracellular region. KEGG pathway analysis indicates that the genes were significantly enriched in Cytokine-cytokine receptor interaction, IL-17 signaling pathway, Rheumatoid arthritis and TNF signaling pathway. In combination with the results of the protein-protein interaction (PPI) network and CytoHubba, 10 hub genes including IL1B, CXCL8, CXCL10, CXCL1, CXCL2, CXCL5, ICAM1, IL1RN, TIMP1 and MMP3 were selected. Based on the DEG-miRNAs network construction, 5 miRNAs including hsa-mir-21-5p, hsa-mir-93-5p, hsa-mir-98-5p, hsa-mir-1-3p and hsa-mir-335-5p were identified as potential critical miRNAs. 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