title: Genetic variation in DROSHA 3'UTR regulated by hsa-miR-27b is associated with bladder cancer risk.
abstract: OBJECTIVE
  miRNAs can regulate the biological processes, including differentiation, proliferation and apoptosis. DICER and DROSHA are two members of RNase III family, playing pivotal roles in the pathway of miRNAs biogenesis. In this study, we hypothesized that genetic variations of the DICER and DROSHA genes were associated with the bladder cancer risk.
  
  
  METHODS
  We performed a case-control study of 685 bladder cancer cases and 730 controls to investigate the association between the seven functional SNPs of DICER and DROSHA genes and bladder cancer risk. We then evaluated the functionality of the important SNPs.
  
  
  RESULTS
  We found that rs10719T>C polymorphism located in 3' untranslated region (UTR) of DROSHA gene was associated with the increased risk of bladder cancer. Stratified analysis suggested that rs10719TC/CC genotype can increase risk of bladder cancer among male patients (Adjusted OR = 1.34, 95% CI = 1.05-1.70, P = 0.018), and ever smokers (1.56, 1.14-2.14, 0.006), compared with TT genotype. Furthermore, DROSHA rs10719T>C polymorphism was predicted to regulate the binding activity of hsa-miR-27a/b. Luciferase reported gene assay confirmed that rs10719 T to G substitution disrupted the binding site for hsa-miR-27b, resulting the increased levels of DROSHA protein.
  
  
  CONCLUSIONS
  Taken together, these findings suggested that DROSHA rs10719T>C polymorphism may be associated with bladder cancer risk in a Chinese population, and hsa-miR-27b can influence the expression of DROSHA protein by binding with 3'UTR.
authors: Department of Urology, Jiangsu Province Hospital of TCM, Nanjing, China ; State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, China.
authors: Lin
authors: L
authors: Yuan
authors: Haiyan
authors: H
authors: Chu
authors: Meilin
authors: M
authors: Wang
authors: Xiaojian
authors: X
authors: Gu
authors: Danni
authors: D
authors: Shi
authors: Lan
authors: L
authors: Ma
authors: Dongyan
authors: D
authors: Zhong
authors: Mulong
authors: M
authors: Du
authors: Pu
authors: P
authors: Li
authors: Na
authors: N
authors: Tong
authors: Guangbo
authors: G
authors: Fu
authors: Chao
authors: C
authors: Qin
authors: Changjun
authors: C
authors: Yin
authors: Zhengdong
authors: Z
authors: Zhang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D000368:Aged; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D001665:Binding Sites; D016022:Case-Control Studies; D053487:DEAD-box RNA Helicases / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D043244:Ribonuclease III / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; C531388:MIRN27 microRNA, human; D035683:MicroRNAs; C408087:DICER1 protein, human; C517918:DROSHA protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases