Abstract
MicroRNAs (miRNAs) are small single-stranded non-protein-coding RNA molecules, of 22-25 nucleotides in length, functioning as negative post- transcriptional gene regulators in animals, plants and viruses. Recent evidences showed that miRNA expression has been implicated in tumorigenesis, and indicates that miRNAs might function as tumour suppressors and oncogenes. We hypothesized that single nucleotide polymorphisms (SNPs) within the 3’UTR can alter the bond between miRNAs and their targets, affecting gene regulation and the individual risk of developing cancer. In order to test our hypothesis, we selected the 3’UTRs of 69 genes linked to the development of colorectal cancer and, through specific algorithms, we predicted their possible miRNAs target sites.
We identified 26 polymorphisms in predicted target sites and we calculated the difference of the variation of the Gibbs binding free energy (∆∆G) between the two alleles of each SNP. Thus, using this measurement, we ranked the SNPs for their ability to alter miRNA-target interaction. On the basis of this ranking, we selected the three more active polymorphisms (one located in GALNS and two located in PKNOX1) and we carried out a case-control association study on 224 cases of
colorectal cancer and 226 controls. After genotyping the polymorphisms by allele- specific PCRs, we implemented a logistic regression analysis. We didn’t find any statistically significant association between the polymorphisms and the risk of developing colorectal cancer. Nevertheless, following linkage disequilibrium analysis, we found a statistically significant association between one of the diplotypes of PKNOX1 and the increased risk of colorectal cancer. These data seem to verify the starting hypothesis and encourage to investigate further on this topic.
