OncoTargets and Therapy (Nov 2016)
Genetic variation rs7930 in the miR-4273-5p target site is associated with a risk of colorectal cancer
Abstract
Ah-Reum Lee,1 Jongkeun Park,1 Keum Ji Jung,2 Sun Ha Jee,2 Sungjoo Kim-Yoon1 1Department of Medical Life Sciences, The Catholic University of Korea, Seoul, South Korea; 2Department of Epidemiology and Health Promotion, Institute for Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, Republic of Korea Purpose: MicroRNAs (miRNAs) are noncoding RNAs that play roles as tumor suppressors or oncogenes by regulating the expression of target genes via binding to seed-match sequences. Polymorphisms in the miRNA-binding site of a target gene can alter miRNA binding and potentially affect the risk of cancer. The objective of this study was to identify single-nucleotide polymorphisms (SNPs) in miRNA-binding sites and assess their involvement in the risk of colorectal cancer (CRC). Materials and methods: SNPs in the 3' untranslated regions of genes were selected and assessed for their effects on CRC risk in Korean population using participants in Korean Cancer Prevention Study-II. A detailed study was carried out with the SNP rs7930 in the 3' untranslated region of the translocase of outer mitochondrial membrane 20 (TOMM20) gene. A case–control study (1,545 controls and 620 CRC cases) was conducted to analyze the relationship between polymorphism at rs7930 and the risk of CRC. An interacting miRNA was predicted using web-based software programs, and its interaction with rs7930 in CRC cell lines was investigated by using a luciferase assay. Results: Individuals carrying the rs7930 AG genotype (G allele) had a 1.721-fold increased risk for CRC in comparison with those with the AA genotype (A allele). The miRNA miR-4273-5p was found to specifically interact with the A allele of rs7930 and to suppress the expression of the target gene (TOMM20) in CRC cell lines. Conclusion: rs7930 is an independent genetic risk factor for CRC susceptibility. Our study suggests a mechanism of how this SNP contributes to CRC carcinogenesis. Keywords: colorectal cancer, miR-4273-5p, SNP, rs7930, frequency, susceptibility
