Construction and Bioinformatics Analysis of the miRNA-mRNA Regulatory Network in Diabetic Nephropathy

Abstract

Background: MicroRNA (miRNA) has been confirmed to be involved in the occurrence, development, and prevention of diabetic nephropathy (DN), but its mechanism of action is still unclear.

Objective: With the help of the GEO database, bioinformatics methods are used to explore the miRNA-mRNA regulatory relationship pairs related to diabetic nephropathy and explain their potential mechanisms of action.

Methods: The DN-related miRNA microarray dataset (GSE51674) and mRNA expression dataset (GSE30122) are downloaded through the GEO database, online analysis tool GEO2R is used for data differential expression analysis, TargetScan, miRTarBase, and miRDB databases are used to predict potential downstream target genes regulated by differentially expressed miRNAs, and intersection with differential genes is used to obtain candidate target genes. According to the regulatory relationship between miRNA and mRNA, the miRNA-mRNA relationship pair is clarified, and the miRNA-mRNA regulatory network is constructed using Cytoscape. DAVID is used to perform GO function enrichment analysis and KEGG pathway analysis of candidate target genes. By GeneMANIA prediction of miRNA target genes and coexpressed genes, the protein interaction network is constructed. Results and Conclusions. A total of 67 differentially expressed miRNAs were screened in the experiment, of which 42 were upregulated and 25 were downregulated; a total of 448 differentially expressed mRNAs were screened, of which 93 were upregulated and 355 were downregulated. Using TargetScan, miRTarBase, and miRDB databases to predict downstream targets of differentially expressed miRNAs, 2283 downstream target genes coexisting in 3 databases were predicted to intersect with differentially expressed mRNAs to obtain 96 candidate target genes. Finally, 44 miRNA-mRNA relationship pairs consisting of 12 differentially expressed miRNAs and 27 differentially expressed mRNAs were screened out; further analysis showed that miRNA regulatory network genes may participate in the occurrence and development of diabetic nephropathy through PI3K/Akt, ECM-receptor interaction pathway, and RAS signaling pathway.