Methods

Screening of miRNAs and genes
Extensive literature search and exploration of online databases were conducted to understand miRNAs mediated regulation of solid cancer associated target genes using miRCancer (http://mircancer.ecu.edu/) and miRDisease (http://mir2disease.org). miRNAs and target genes were screened by following two criteria: (1) only up regulated oncogenes or down regulated tumor suppressor genes were selected and (2) the screening was performed by selecting oncogenes and tumor suppressor genes as target genes when both of them are either up regulated or down regulated. Further, minimum free energy (MFE) score based binding affinity between miRNAs and their target genes were explored and inspected using miRTarbase web server (http://mirtarbase.mbc.nctu.edu.tw/). Furthermore, the involvement of target genes in different biological function was inspected using UniProt (http://www.uniprot.org/) web server and plotted using Venn (http://bioinformatics.psb.ugent.be/webtools/Venn/) diagram.

Prediction of structural model of miRNA-mRNA complexes
To verify the folding affinity between selected miRNAs and their target genes, secondary structures were predicted using RNAfold web server (http://rna.tbi.univie.ac.at/cgi-bin/RNAfold.cgi). The resulted dot bracketed structures of duplex were used for prediction of their tertiary structure using RNA COMPOSER (http://rnacomposer.cs.put poznan.pl/).

Structure extraction of AGO protein
The three-dimensional structure of AGO protein was retrieved from Protein Data Bank (PDB ID: 3F73). The structure preparation and correction of AGO protein were performed using Discovery Studio 3.5 suite (http://accelrys.com/products/discovery-studio/visualizatation-download.php).

Molecular docking between miRNA-mRNA and AGO protein
Docking between three dimensional structure of protein and ligand, may be a biomolecule like miRNA or a gene is an efficient computational method to inspect the molecular interaction [61]. Docking were performed between AGO protein and miRNA-mRNA duplexes (miR-106 and PTEN; miR-21 and TGFBR2; and miR-29b-2 and VEGFA) using PatchDock web server (http://bioinfo3d.cs.tau.ac.il/PatchDock/),algorithm ranked the docked complexes on the basis of highest geometrical shape complementary scores. The molecular interaction was studied using Discovery Studio 3.5 suite.