Genetic variations in miR-27a gene decrease mature miR-27a level and reduce gastric cancer susceptibility

Abstract

MicroRNAs (miRNAs) are noncoding RNAs that function as post-transcriptional regulators of tumor oncogenes and suppressors. Single-nucleotide polymorphisms (SNPs) in miRNA genes are a novel class of genetic variations in the human genome that are currently being identified and investigated in human cancers. In this study, we aimed to investigate whether SNPs in the miR-27a gene affect miR-27a expression and alter susceptibility to gastric cancer. Therefore, we conducted a case-control population study and the allele and genotype frequencies for polymorphism rs11671784 in miR-27a gene were examined in the study population. As a result, we found that the G/A polymorphism in the miR-27a gene exhibited a significant effect on gastric cancer risk. Compared with GG homozygotes, subjects who were GA heterozygotes or AA homozygotes exhibited a decreased risk of gastric cancer. The G/A polymorphism impaired the processing of pre-miR-27a to mature miR-27a, resulting in significantly reduced expression of mature miR-27a and an increased level of its target HOXA10. Furthermore, we confirmed these findings in in vitro studies by overexpressing pre-miR-27a carrying G or A allele. It provided further evidence demonstrating that allelic difference of rs11671784 is linked to gastric tumorigenesis. In summary, our results indicate that the G/A polymorphism in miR-27a gene (rs11671784) decreases miR-27a expression, reduces gastric cancer risk and plays a role in gastric tumorigenesis. This is the first study to address the role and function of miR-27a polymorphism rs11671784 in gastric cancer. These results could be useful to assess individual susceptibility of gastric cancer and will improve our understanding of the potential contribution of miRNA SNPs to cancer pathogenesis.