TRAIL and EGFR Pathways Targeting microRNAs are PredominantlyRegulated in Human Diabetic Nephropathy

Background: Unbiased microRNA profiling of renal tissue and urinary extracellular vesi-cles (uEVs) from diabetic nephropathy (DN) subjects may unravel novel targets with diagnostic and therapeutic potential. Here we used the miRNA profile of uEVs and renal biopsies from DN subjects available on the GEO database. Methods: The miR expression profiles of kidney tissue (GSE51674) and urinary exosomes (GSE48318) from DN and control subjects were obtained by GEO2R tools from Gene Expression Om-nibus (GEO) databases. Differentially expressed miRNAs in DN samples, relative to controls, were identified using a bioinformatic pipeline. Targets of miRs commonly regulated in both sample types were predicted by miRWalk, followed by functional gene enrichment analysis. Gene targets were iden-tified by MiRTarBase, TargetScan and MiRDB. Results: Eight miRs, including let-7c, miR-10a, miR-10b and miR-181c, were significantly regulated in kidney tissue and uEVs in DN subjects versus controls. The top 10 significant pathways targeted by these miRs included TRAIL, EGFR, Proteoglycan syndecan, VEGF and Integrin Pathway. Gene target analysis by miRwalk upon validation using ShinyGO 70 targets with significant miRNA-mRNA inter-action. Conclusion: In silico analysis showed that miRs targeting TRAIL and EGFR signaling are predomi-nately regulated in uEVs and renal tissue of DN subjects. After wet-lab validation, the identified miRs- target pairs may be explored for their diagnostic and/or therapeutic potential in diabetic nephropathy.