In-Silico Analysis of rSNPs in miRNA:mRNA Duplex Involved in Insulin Signaling Genes Shows a Possible Pathogenesis of Insulin Resistance.

Abstract

Insulin resistance is a condition in which the body produces insulin but is unable to use it effectively. Aberrations in insulin signaling are known to play a crucial role in the pathogenesis of this disease state. Eventually, patients will have glucose build-up in their blood instead of being absorbed by the cells, leading to type 2 diabetes. In the current study, we focus on understanding the role of rSNP mediated miRNA:mRNA dysregulation and its impact on the above metabolic condition. More than 30 genes involved in the insulin signaling pathway were found using the KEGG database. The 3'UTR end of genes was studied by using RegRNA and Ensembl, whereas TargetScan along with miRbase were used to identify their target miRNAs. Binding free energy was used as a parameter to analyze the effect of polymorphism on the miRNA:mRNA duplex formation. Further, the UNA fold was used to determine the heat capacity changes. The genes INSR, INS, GLUT4, FOXO1, IL6, TRIB3, and SREBF1, were selected for analysis. Multiple miRNAs, hsa-miR-16-5p, hsa-miR-15a-15p were identified in the SNP occurring region for INSR. INS, too, showed similar results. INSR, INS, and TRIB3 were found to have the maximum change in their binding free energy due to rSNP variation. A destabilisation in the heat capacity values was observed too, which contributed due to rSNP induction. A direct relationship between miRNA target polymorphism and the stability of the miRNA:mRNA duplex was observed. The current methodology used to study insulin resistance pathogenesis could elaborate on our existing knowledge of miRNA-mediated disease states.