A Catalog of Polymorphisms Falling in MicroRNA-Binding Regions of Cancer Genes

Recent evidence indicates that small, nonprotein-coding RNA molecules, called microRNAs (miRNAs), control cell growth, differentiation, and apoptosis, and are also involved in tumorigenesis. miRNAs can bind to the 3′ untranslated regions (3′UTRs) of messenger RNAs and interfere with their translation. We hypothesized that common polymorphisms within their genes or within their targets could have an important impact for an individual's risk to develop complex diseases. In this study, we selected the 3′UTRs of 129 genes involved in pathways commonly acknowledged as important for cancer, and we identified putative miRNA-binding sites by means of specialized algorithms (PicTar, DIANA-MicroT, miRBase, miRanda, TargetScan, and MicroInspector). Then we investigated 79 single-nucleotide polymorphisms (SNPs) within the putative binding sites for their ability to affect or impair the binding with the miRNA by assessing the ΔΔG, the variation of ΔG (Gibbs free energy), through comparing the wild-type and their corresponding variant alleles. Moreover, we reported seven identified SNPs in seven pre-miRNA hairpin regions and one SNP in the mature sequence of miR-608. Considering the validation status of the SNPs and their frequencies, we found at least 23 candidate polymorphisms of biological relevance that we propose for further investigation in case-control association studies.