Abstract

MicroRNAs are small endogenous regulatory RNAs that are involved in the control of multiple biological pathways. Allele variants in microRNAs are known to contribute to disease by affecting either microRNA expression or function. We have previously identified an association of rs12416605:C/T, in the seed region of miR-938, with the diffuse subtype of gastric cancer and aimed to investigate the functional effect of this SNP. To test the influence of rs12416605:C>T in miR-938 expression, either the C or T miR-938 alleles were transfected in HeLa cells and miR-938 expression was measured by RT- qPCR. The rs12416605 C allele was 1.5 times more abundant than the T allele (Student t-test, p-value < 0.05) indicating that rs12416605 may affect the expression of miR-938. Furthermore, to investigated the effect of rs12416605:C/T on the spectrum of miR-938 target genes, transcriptome analyses on HeLa cells over-expressed with either the C or T rs12416605 alleles were performed. From approximately 500 deregulated transcripts, around 50% were exclusively regulated by one or the other rs12416605:C>T alleles. Additionally, even though both variants presented cancer as the top disease associated with their deregulated genes (Ingenuity Pathway Analysis), several genes implicated in the aetiology of gastric cancer, such as the Fibroblast Growth Factor Receptor 1 (FGFR1), the NK2 Homeobox 8 gene (NKX2-8) and the chemokine CXCL12 genes, were specifically deregulated by only one of the rs12416605:C>T alleles and were predicted as miR-938 allele specific targets. All together suggests that rs12416605 may be involved in gastric cancer susceptibility by affecting the regulatory function of miR-938.