Abstract

The present study aims to identify the circulatory microRNAs (miRNAs) that are overexpressed in pre-diabetes and Type 2 diabetes mellitus (T2DM) condition that can serve as potential biomarkers and to investigate the candidate miRNA-target interactions in insulin signal transduction pathway at the molecular level by employing in silico approach. Using miRNA-target prediction tools miRDB, TargetScan, microT-CDS, and miRmap, 17 miRNAs were selected that could downregulate the insulin receptor (INSR) and INSR substrate 1(IRS-1) genes. Only experimentally validated miRNAs were selected using miTarBase. The shortlisted circulatory miRNAs miR-15b-5p, miR-195-5p, miR-7-5p, miR-144-3p, and miR-148a-3p underwent miRNA-target enrichment analysis and network analysis using the bioinformatic tool MIENTURNET. The miRNA-mRNA complex structures were predicted using RNAfold web server and RNA Composer. Finally, 5 miRNAs having good binding affinity with the target proteins were docked using HNADOCK and the docked complexes were visualized using Discovery Studio Visualizer. Based on in silico analysis, it is evident that INSR is the target gene for miR-15b-5p/miR-195-Sp/miR-424-5p and IRS-1 is the target gene for miR-15b-5p/miR-195-5p/miR-424-5p and miR-30d-5p. Our results could categorize miRNAs that could target the INSR and IRS-1 located upstream of the insulin signal transduction pathway and further could be used to explore their clinical significance in pre-diabetes and T2DM.

Key words: Type 2 diabetes, Insulin signaling pathway, in silico approach, biomarkers, miRNA-target prediction, molecular docking