Identification of miRNA-Target Gene-Transcription Factor Regulatory Network as Functional Motifs Involved in Glomerular Diabetic Nephropathy

Abstract

The gene regulatory approach based on retrieving information from the database provides a detailed characterization of the molecular mechanisms of disease progression at the level of miRNAs, Transcription Factors (TFs), and genes. Moreover, gene regulatory networks can find an interaction between the miRNAs, TFs, and genes involved in diabetic nephropathy (DN), but the underlying mechanisms of motif remain unclear. We first gathered genes related to glomeruli diabetic nephropathy from GEO and CTD database. Besides, miRNAs targeting genes were collected from the public databases and GEO. Furthermore, regulator TFs were accumulated from related public databases. After that, we explored the regulatory relationships between TF-miRNA, miRNA-Gene, TF-Gene, and miRNA–TF using FANMOD software. Finally, a gene regulatory network consisting of miRNAs, genes, and TFs was constructed, helping the Cytoscape. The global const parameter in FANMOD software used to discover the interaction between miRNAs, genes, TFs, and 3-node regulatory motif types were detected in the resulting network. Among them, it led to the discovery of the two-node feedback motif (2FB) in charge of the up-regulation of miRNA-target gene-TF and TF-mediated cascade motif and co-pointing motif (COP) responsible for the down-regulation of miRNA-target gene–TF. In this study, we found a correlation between miRNAs, TFs, and target genes using a gene regulatory network. We revealed the candidate 3-node motifs associated with the progression of DN. Therefore, detected molecular mechanisms, as well as the relationship between previous studies, demonstrated targets that can help in the discovery of a novel treatment for DN.