Title:In-Silico Analysis of rSNPs in miRNA:mRNA Duplex Involved in Insulin
Signaling Genes Shows a Possible Pathogenesis of Insulin Resistance
Volume: 10
Issue: 3
Author(s): Jithin S. Sunny and Lilly M. Saleena*
Affiliation:
- Department of Biotechnology, SRM Institute of Science and Technology, SRM Nagar, Kattankulathur 603203, Kanchipuram, Chennai TN,India
Keywords:
miRNA, mRNA, insulin resistance, ensembl, miRNA:mRNA hybrid, binding energy.
Abstract:
Background: 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.
Objective: In the current study, we focus on understanding the role of rSNP mediated miRNA:mRNA
dysregulation and its impact on the above metabolic condition.
Methods: 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.
Results: 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.
Conclusion: 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.
