Genetic variation rs7930 in the miR-4273-5p target site is associated with a risk of colorectal cancer
Authors Lee AR, Park J, Jung KJ, Jee SH, Kim-Yoon SJ
Received 18 March 2016
Accepted for publication 20 May 2016
Published 7 November 2016 Volume 2016:9 Pages 6885—6895
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Ram Prasad
Peer reviewer comments 2
Editor who approved publication: Dr William Cho
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
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