Rs1347093 regulates microRNA-216/-217 expression and is associated with pancreatic cancer risk

Background: Single nucleotide polymorphism (SNP) rs1347093 shows statistically significant association with lung cancer risk, but there is no further rs1347093 expression quantitative trait loci (eQTL) effect information. SNP rs1347093 is located in microRNA-216/-217 (miR-216/-217) locus. In addition, miR-216/-217 have pancreas-enriched expressions. In this study, we examined a potential miR-216/-217 promoter region, and investigated the effect of rs1347093-A allele on the miR-216/-217 promoter activity.

Methods: Bioinformatics analysis, quantitative real-time PCR, luciferase reporter assay, Western blotting, and cell counting kit-8 (CCK-8) assay were performed.

Results: The miR-216/-217 expressions are down-regulated in pancreatic cancer. In pancreatic cancer patients carrying the rs1347093-A allele, miR-216/-217 expressions were more largely suppressed. We identified a potential promoter region in miR-216/-217 locus and further showed that rs1347093-A allele resulted in significantly reduced promoter activity in pancreatic cancer cells, which could be mediated by MEF2C activities. In terms of mechanism in the pathogenesis of pancreatic cancer, miR-216b-5p expression was down-regulated, thereby preventing it from interacting with beclin-1 mRNA while promoting the survival of pancreatic cancer cells.

Conclusions: This study may reveal the biological relevance underlying rs1347093-A allele with an increase in pancreatic cancer risk. SNP rs1347093 could be meaningful as a novel biomarker for pancreatic cancer risk.