title: A Functional Polymorphism in the Promoter of MiR-143/145 Is Associated With the Risk of Cervical Squamous Cell Carcinoma in Chinese Women: A Case-Control Study.
abstract: MiR-143/145 is down-regulated in cervical cancer, which may serve as a tumor suppressor by targeting KRAS and Ras-responsive element-binding protein (RREB1). Activated KRAS leads to down-regulation of miR-143/145 transcription in a RREB1-dependent manner, establishing a miR-143/145-KRAS-RREB1 feedback loop. A polymorphism rs4705343C/T in the promoter of miR-143/145 might influence the binding of TATA-binding protein. We hypothesized that the miR-143/145 rs4705343 and KRAS rs712 may be related to the occurrence of cervical squamous cell carcinoma (CSCC). In this study, we genotyped the 2 polymorphisms in 415 patients with CSCC and 504 controls using polymerase chain reaction-restriction fragment length polymorphism. The promoter activities were measured by the Dual-Luciferase Reporter Assay System. We found that the rs4705343TC genotype was associated with an increased risk of CSCC (adjusted odds ratio [OR] = 1.37; 95% confidence interval [CI], 1.05-1.80). The significantly increased association was also observed in a dominant genetic model (adjusted OR = 1.32; 95% CI, 1.01-1.72). Combined analysis showed that individuals carrying the genotypes of rs4705343 TC/CC and rs712GT/TT had a 1.47-fold increased risk of CSCC (adjusted OR = 1.47; 95% CI, 1.01-2.15). By using multifactor dimensionality reduction software method, we identified a significant interaction between the miR-143/145 rs4705343 and KRAS rs712. Dual-Luciferase Reporter Assay showed that the luciferase activity was significantly lower in cells transfected with the rs4705343C allele than that of the rs4705343T allele. These findings indicate that miR-143/145 rs4705343 and KRAS rs712 may contribute to the etiology of CSCC in Chinese women.
authors.affiliation: From the Laboratory of Molecular and Translational Medicine, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, P.R. China (YL, RS, LL, FY, XN, LZ, LG); Key Laboratory of Obstetric and Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Chengdu, Sichuan, P.R. China (YL, RS, LL, FY, XN, LZ, LG); Central Laboratory, Yunnan University of Chinese Traditional Medicine, Kunming, Yunnan, P.R. China (RS); and Department of Forensic Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan, P.R. China (LW, PC, LZ).
authors.forename: Yundan
authors.initials: Y
authors.lastname: Liang
authors.forename: Ruifen
authors.initials: R
authors.lastname: Sun
authors.forename: Lijuan
authors.initials: L
authors.lastname: Li
authors.forename: Fang
authors.initials: F
authors.lastname: Yuan
authors.forename: Weibo
authors.initials: W
authors.lastname: Liang
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Xinwen
authors.initials: X
authors.lastname: Nie
authors.forename: Peng
authors.initials: P
authors.lastname: Chen
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Linbo
authors.initials: L
authors.lastname: Gao
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D016022:Case-Control Studies; D002681:China; D005260:Female; D005838:Genotype; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D002583:Uterine Cervical Neoplasms / Q000235:genetics*; D018631:ras Proteins / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; C542359:MIRN143 microRNA, human; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins