机构：[1]Laboratory 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[2]Central Laboratory, Yunnan University of Chinese Traditional Medicine, Kunming 650500, Yunnan, P.R. China[3]Department of Pathology and Pathophysiology, Chengdu Medical College, Chengdu, Sichuan 610083, P.R. China[4]Division of Reproductive Medical Center, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China[5]Department of Child Health, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China
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.
基金：
the National Natural Science Foundation of China (no. 81302149), the Science & Technology Pillar Program of Sichuan Province (no. 2016SZ0013), and the Ph.D. Programs Foundation of Ministry of Education of China (no. 20130181120011).
语种：
外文
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出版当年[2017]版：
大类|2 区医学
小类|2 区肿瘤学3 区细胞生物学
最新[2023]版：
无
第一作者：
第一作者机构：[1]Laboratory 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[2]Central Laboratory, Yunnan University of Chinese Traditional Medicine, Kunming 650500, Yunnan, P.R. China
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通讯作者：
推荐引用方式(GB/T 7714)：
Sun Ruifen,Liang Yundan,Yuan Fang,et al.Functional polymorphisms in the promoter region of miR-17-92 cluster are associated with a decreased risk of colorectal cancer.[J].Oncotarget.2017,8(47):82531-82540.doi:10.18632/oncotarget.19753.
APA：
Sun Ruifen,Liang Yundan,Yuan Fang,Nie Xinwen,Sun Hong...&Zhang Lin.(2017).Functional polymorphisms in the promoter region of miR-17-92 cluster are associated with a decreased risk of colorectal cancer..Oncotarget,8,(47)
MLA：
Sun Ruifen,et al."Functional polymorphisms in the promoter region of miR-17-92 cluster are associated with a decreased risk of colorectal cancer.".Oncotarget 8..47(2017):82531-82540
