Functional polymorphisms in the promoter region of miR-17-92 cluster are associated with a decreased risk of colorectal cancer
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Ruifen Sun1,2,*, Yundan Liang3,*, Fang Yuan1,4, Xinwen Nie1, Hong Sun1,4, Yanyun Wang1, Tao Yu5, Linbo Gao1 and Lin Zhang1
1Laboratory of Molecular and Translational Medicine, West China Institute of Women and Children’s Health, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China
2Central Laboratory, Yunnan University of Chinese Traditional Medicine, Kunming 650500, Yunnan, P.R. China
3Department of Pathology and Pathophysiology, Chengdu Medical College, Chengdu, Sichuan 610083, P.R. China
4Division of Reproductive Medical Center, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China
5Department of Child Health, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China
*These authors have contributed equally to this work
Linbo Gao, email: [email protected]
Lin Zhang, email: [email protected]
Keywords: miR-17-92, promoter, polymorphism, luciferase activity, colorectal cancer
Received: May 07, 2017 Accepted: June 19, 2017 Published: July 31, 2017
miR-17-92 cluster is identified as a potential oncogenic miRNA. The aim of this study was to investigate the association of polymorphisms in the promoter region of miR-17-92 cluster with the risk of colorectal cancer (CRC). Three polymorphisms (i.e., rs9588884, rs982873 and rs1813389) in the promoter of miR-17-92 were analyzed among 874 cases and 1132 controls using a TaqMan allelic discrimination assay or a polymerase chain reaction-restriction fragment length polymorphism method. Relative expression of miR-17-92 was examined among CRC tumors and noncancerous tissues using quantitative reverse transcription-PCR. Transcriptional activities were measured using dual-luciferase reporter assay. We found a significantly reduced CRC risk with the rs9588884 (GG vs. CC: adjusted OR = 0.46, 95% CI, 0.35-0.62; dominant model: adjusted OR = 0.72, 95% CI, 0.59-0.86; recessive model: adjusted OR = 0.53, 95% CI, 0.40-0.69) and the rs982873 (CC vs. TT: adjusted OR = 0.60, 95%CI, 0.46-0.80; recessive model: adjusted OR = 0.62, 95% CI, 0.49-0.80). Haplotype analysis showed that the GCG haplotype had a decreased risk for CRC compared to the CTA haplotype (adjusted OR = 0.67, 95% CI, 0.57-0.79). The rs9588884 GG displayed a lower level of miR-20a and the rs982873 CC displayed a lower level of miR-17. Additionally, the rare allele of rs9588884 G and the rs982873 C revealed a reduced luciferase activity. These findings indicate that the rs9588884 GG and the rs982873 CC in the promoter of miR-17-92 may protect against CRC, possibly by decreasing transcriptional activity and eventually resulting in lower levels of miR-20a and miR-17.
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