In Silico Prediction of NOS2, NOS3 and Arginase 1 Genes Targeting by Micro RNAs Upregulated in Systemic Sclerosis

Abstract

Introduction: Systemic sclerosis (SSc) is a chronic disorder, characterised by endothelial dysfunction and fibrosis of skin and internal organs. Endothelium dysfunction leads to a decrease in nitric oxide levels, consequent to reduced Nitric Oxide synthase 3 (NOS3) activity due to decreased NOS3 gene function. Besides endothelium, macrophages too play an important role in the pathogenesis of SSc; classically activated M1 macrophages (express NOS2) and alternatively activated M2 macrophages (express Arginase1) are differentially altered in favour of M2 macrophages. Micro-RNAs (miRNAs) regulate expression of various genes and may favour disease phenotype. Aim: Our aim was to identify differentially expressed micro-RNAs in SSc, which target NOS2, NOS3 and Arginase1 genes by in-silico approach. Methods: Data on miRNAs upregulation reported in various studies was collected and their sequence ID from miRBase was identified in FASTA format from NCBI. Binding strength of these miRNAs against NOS2, NOS3 and Arginase1 genes was evaluated by RNA22. Results: After scanning 39 publications reporting miRNA expression in SSc, a total of 13 miRNAs were found to be up-regulated for NOS2 (Gibbs free energy ≤18.0Kj/mol) and 15 miRNAs up-regulated for NOS3 (Gibbs free energy ≤18.0Kj/mol) whereas for Arginase1 only 2 miRNAs were up-regulated. Conclusion: There is differential upregulation of miRNAs in SSc. Micro RNAs targeting NOS2 and NOS3 genes are highly up-regulated in comparison to Arginase 1. Role of epigenetic regulation of genes by miRNAs may play a key role in pathogenesis of SSc.