A functional variant in miR-143 promoter contributes to prostate cancer risk

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A functional variant in miR-143 promoter contributes to prostate cancer risk

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作者：Haiyan Chu ; Dongyan Zhong ; Jialin Tang ; Jie Li ; Yao Xue ; Na Tong…
关键词：miR ; 143 ; Prostate cancer ; KLK2 ; Genetic susceptibility ; Molecular epidemiology
刊名：Archives of Toxicology
出版年：2016
出版时间：February 2016
年：2016
卷：90
期：2
页码：403-414
全文大小：862 KB
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作者单位：Haiyan Chu (1) (2) (3)
Dongyan Zhong (3) (4)
Jialin Tang (3) (5)
Jie Li (6)
Yao Xue (2) (3)
Na Tong (2) (3)
Chao Qin (6)
Changjun Yin (6)
Zhengdong Zhang (1) (2) (3)
Meilin Wang (1) (2) (3)

1. State Key Laboratory of Reproductive Medicine, Nanjing Medical University, 818 East Tianyuan Road, Nanjing, 211166, China
2. Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, China
3. Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China
4. Orthopaedic Institute, Soochow University, Suzhou, China
5. Department of Public Health, Jiangxi Center for Disease Control and Prevention, 555 Beijing East Road, Nanchang, 330029, Jiangxi, China
6. Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
刊物主题：Pharmacology/Toxicology; Occupational Medicine/Industrial Medicine; Environmental Health; Biomedicine general;
出版者：Springer Berlin Heidelberg
ISSN：1432-0738

文摘

MicroRNAs are important regulators in numerous cellular processes, including cell differentiation, proliferation, and apoptosis. Recently, miR-143 was identified as a tumor suppressor in prostate cancer (PCa). To explore the mechanism of dysregulation and anti-tumor function of miR-143 in PCa, we first found a single-nucleotide polymorphism rs4705342T>C in the promoter region of miR-143 through bioinformatics tools and then performed a case–control study including 608 PCa patients and 709 controls. Results suggested that subjects with TC/CC genotypes had significantly decreased risk of PCa compared with those with TT genotype (adjusted OR 0.68, 95 % CI 0.55–0.85). Further functional assays showed that the risk-associated T allele increased the protein-binding affinity and reduced the activity of the promoter compared with C allele. In addition, restoration of miR-143 by mimics in PCa cells significantly inhibited cell proliferation and migration and down-regulated the expression level of kallikrein-related peptidase 2 (KLK2) mRNA and protein. The miR-143-KLK2 axis was also confirmed by luciferase reporter assay in vitro. In conclusion, our findings demonstrate that there is the significant association between the functional promoter variant rs4705342T>C in miR-143 and PCa risk and newly describe the miR-143-KLK2 interaction which provided another potential mechanism for miR-143 anti-tumor function. Keywords miR-143 Prostate cancer KLK2 Genetic susceptibility Molecular epidemiology