Modular analysis of target genes of microRNAs in plasma of coal-burning fluoride exposed population based on protein-protein interaction network / 中华地方病学杂志

ABSTRACT

Objective:To establish a protein-protein interaction (PPI) network of 5 microRNA (miRNA) target genes differentially expressed in the plasma of coal-burning fluoride exposed population, and to screen genes and gene modules with important roles.Methods:Five miRNA (hsa-miRNA-3131, hsa-miRNA-4516, hsa-miRNA-6501-5p, hsa-miRNA-10b-5p, hsa-miRNA-4683) target genes differentially expressed in the plasma of coal-burning fluoride exposed population screened by our previous study were mapped to the STRING online database (https//string-db.org), and the PPI network was screened. The Cytoscape v3.6.0 software was used to visualize the PPI network, the topological attribute values degree and betweenness centrality were obtained by the NetworkAnalyzer plug-in, and the central node was filtered in the network (the node with the highest degree and the highest betweenness centrality). At the same time, the maximal clique centrality (MCC) analysis method in the CytoHubba plug-in was used to determine the important nodes in the PPI network. The cluster analysis was conducted by the MCODE plug-in, and the gene modules were screened in the PPI network. The protein names contained in the gene modules were submitted online to the KOBAS v3.0 database (http//kobas.cbi.pku.edu.cn/), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed on the gene modules selected by the MCODE plug-in.Results:The PPI network of target genes was consisted of 1 035 nodes and 4 346 edges. The degree (101) and betweenness centrality (0.010 723 89) of ubiquitin A-52 residue ribosomal protein fusion product 1 (UBA52) were the highest, which was the central node of the PPI network. According to MCC analysis, UBA52 was an important node in the PPI network. The top 5 gene modules were selected from the PPI network, and the highly enriched gene pathways in the KEGG pathway enrichment analysis of the 5 gene modules included ubiquitin mediated proteolysis, spliceosome, endocytosis, neuroactive ligand-receptor interaction and vesicular transport.Conclusion:The PPI network of 5 miRNA target genes differentially expressed in the plasma of people exposed to coal-burning pollution of fluoride is successfully established, and the UBA52 gene and the 5 main pathways of gene modules are selected.