title: A functional variant rs353292 in the flanking region of miR-143/145 contributes to the risk of colorectal cancer.
abstract: MicroRNA (miR)-143 and miR-145 have been identified as molecular regulators in cell proliferation, cell growth, clone formation, apoptosis, cell cycle, invasion, and migration. We previously found that rs353292 in the flanking region of miR-143/145 showed a high frequency in patients with colorectal cancer (CRC). To identify whether the rs353292 polymorphism is a risk factor for CRC, we conducted this study with larger samples. A total of 809 patients with CRC and 1005 gender matched controls were collected. The rs353292 polymorphism was genotyped by using TaqMan allelic discrimination. Dual luciferase reporter assay was carried out to measure the transcriptional activity. We found that the rs353292 polymorphism was associated with an increased risk for developing CRC in heterozygous comparison (adjusted OR = 1.70, 95% CI, 1.32-2.20, P < 0.001), dominant genetic model (adjusted OR = 1.62, 95% CI, 1.26-2.09, P < 0.001), and allele comparison (adjusted OR = 1.46, 95% CI, 1.16-1.84, P = 0.001). The rs353292 CT/TT carriers exhibited a lower expression of miR-143 compared to the CC carriers (P = 0.04). Moreover, the pGL3-rs353292T displayed a significantly lower luciferase activity than pGL3-rs353292C (P < 0.01). These findings indicate that the rs353292 polymorphism is functional and may be a risk factor for the development of CRC.
authors.affiliation: Department of Immunology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Yuan
authors.affiliation: Department of Immunology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, P.R. China.|Central Laboratory, Yunnan University of Chinese Traditional Medicine, Kunming 650500, Yunnan, P.R. China.
authors.forename: Ruifen
authors.initials: R
authors.lastname: Sun
authors.affiliation: Department of Forensic Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Forensic Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Jin
authors.affiliation: Laboratory of Molecular and Translational Medicine, West China Institute of Women and Children's Health; Key Laboratory of Obstetric &Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education; West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Yanyun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Laboratory of Molecular and Translational Medicine, West China Institute of Women and Children's Health; Key Laboratory of Obstetric &Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education; West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Yundan
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Department of Immunology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Guanglu
authors.initials: G
authors.lastname: Che
authors.affiliation: Laboratory of Molecular and Translational Medicine, West China Institute of Women and Children's Health; Key Laboratory of Obstetric &Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education; West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Linbo
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of Immunology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, P.R. China.|Department of Forensic Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, P.R. China.|Laboratory of Molecular and Translational Medicine, West China Institute of Women and Children's Health; Key Laboratory of Obstetric &Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education; West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000072283:A549 Cells; D000483:Alleles; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D045325:HCT116 Cells; D006367:HeLa Cells; D006801:Humans; D008156:Luciferases / Q000235:genetics; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors
chemical_list: C542359:MIRN143 microRNA, human; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D008156:Luciferases