Functional polymorphisms in the promoter region of miR-17-92 cluster are associated with a decreased risk of colorectal cancer
| Autor: | Tao Yu, Linbo Gao, Xinwen Nie, Ruifen Sun, Lin Zhang, Hong Sun, Fang Yuan, Yundan Liang, Yanyun Wang |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Oncology medicine.medical_specialty Colorectal cancer colorectal cancer Child health polymorphism 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Allele luciferase activity Transcriptional activity promoter Traditional medicine business.industry Haplotype miR-17-92 Promoter University hospital medicine.disease 030104 developmental biology 030220 oncology & carcinogenesis Christian ministry business Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Ruifen Sun 1, 2, * , Yundan Liang 3, * , Fang Yuan 1, 4 , Xinwen Nie 1 , Hong Sun 1, 4 , Yanyun Wang 1 , Tao Yu 5 , Linbo Gao 1 and Lin Zhang 1 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 * These authors have contributed equally to this work Correspondence to: Linbo Gao, email: gaolinboscu@163.com Lin Zhang, email: zhanglin@scu.edu.cn Keywords: miR-17-92, promoter, polymorphism, luciferase activity, colorectal cancer Received: May 07, 2017 Accepted: June 19, 2017 Published: July 31, 2017 ABSTRACT 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. |
| Databáze: | OpenAIRE |
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