Role of micro RNA 21 (miR-21) in dengue disease progression and cross talk with target proteins

Previous studies have concluded that miRNAs may be implicated in the pathogenesis of dengue, as upregulated miRNAs were observed in blood and serum samples from infected patients. These biomarkers for dengue infection are highly promising. Among these, microRNA-21 has emerged as a major candidate, although its role in the pathogenesis of dengue infection is not clear. In this study, we predicted the target genes of miR-21 using in silico approaches and modeled guide target duplexes docked to Argonaute protein to hypothesize potential engagement with the RISC in dengue. Potential miR-21 targets and their interacting proteins were identified from public databases. Binding affinities were estimated with the help of miRWalk and miRDB, and expression across the stages of dengue was analyzed based on UniProt. Three-dimensional models of miR-21-mRNA duplexes were derived by RNA Composer and then subjected to molecular docking experiments with AGO (PDB ID: 3F73). Among them, NUDT3, MYRF, and ZNRF1 showed the highest binding affinity and were selected for molecular characterization. The mode of AGO-mediated gene silencing was further explored computationally to assess its regulatory potential. Our findings showed good agreement with previously reported interactions of miR-21 and identified new associations that may contribute to dengue pathogenesis. These genes have strong links to the progression and prognosis of disease and, hence, may serve as a potential therapeutic target. This study supports the development of RNA interference-based strategies targeting the modulation of miR-21 activity for the treatment of dengue.