Investigating the interference of single nucleotide polymorphisms with miRNA mediated gene regulation in pancreatic ductal adenocarcinoma: An in silico approach

Abstract

BackgroundPancreatic ductal adenocarcinoma (PDAC) has a strong genetic component and single nucleotide polymorphisms (SNPs) in key genes have been found to modulate the susceptibility of the individuals to the disease. SNPs in 3′-UTR of the target genes or in miRNA seed region has gained much importance as this may lead to impairment of miRNA-mRNA interaction. Not much information about this phenomenon is available with respect to PDAC and we wanted to predict such SNPs which could affect miRNA function in the disease using bioinformatics tools. MethodsAfter identifying the deregulated miRNAs and genes in PDAC, we determined how many of those altered genes are among experimentally validated targets of those miRNAs. Subsequently, SNPs which could alter these miRNA-mRNA interactions were detected using multiple webtools following high stringent conditions. Disease relevance of the SNPs were also evaluated. ResultsWe identified a total of 2492 experimentally validated target genes for 303 miRNAs deregulated in PDAC. Our meta-analysis from 363 PDAC patients and 162 control individuals resulted in a set of differentially expressed genes in pancreatic cancer, which was further compared with the miRNA target genes to get targets differentially expressed in pancreatic cancer. We further detected SNPs either in ‘seed’ region of miRNAs or ‘seed-match’ sequence of mRNAs either having disruption or creation of miRNA binding site, correlated the expression for each miRNA-SNP-mRNA interaction. Selected SNPs were found to be in LD with important GWAS identified SNPs. ConclusionOur study, hereby, explores the probable effects of SNPs on miRNA-target mRNA interactions. Through stringent analytical methods, we have identified 3 common variants and 13other rare variants possibly interfering with miRNA mediated gene regulation in PDAC.