Abstract
Single nucleotide polymorphisms (SNPs) within binding sites of microRNAs (miRNAs) could modify cancer susceptibility by changing the binding affinity of miRNAs on their target mRNA 3'-untranslated regions (UTRs). MicroRNA-21 (miR-21) is involved in the development of colorectal cancer. However, the relationship between SNPs within the binding sites of miR-21 and colorectal cancer risk has not been widely investigated. A case-control study including 1147 patients and 1203 controls was performed to evaluate the association of SNPs in miR-21 binding sites and colorectal cancer risk. Dual-luciferase reporter assays and functional assays were performed to evaluate the effects of miR-21. The SNP rs6504593 C allele conferred an increased risk of colorectal cancer compared with the T allele in an additive model (odds ratio [OR] = 1.19, 95% confidence interval [CI] = 1.04-1.36, P = 0.011). Dual-luciferase reporter assays demonstrated that the rs6504593 T allele negatively post-transcriptionally regulated IGF2BP1 by altering the binding affinity of miR-21. Additionally, colorectal cancer cells transiently transfected with miR-21 mimics promoted cell proliferation and suppressed apoptosis, whereas inhibition of miR-21 decreased cell growth. These data suggest that the miR-21 binding site SNP rs6504593 in the IGF2BP1 3'-UTR may alter IGF2BP1 expression and contribute to colorectal cancer risk.