title: A microRNA-7 binding site polymorphism in HOXB5 leads to differential gene expression in bladder cancer.
abstract: OBJECTIVE
  To investigate the biological function of HOXB5 in human bladder cancer and explore whether the HOXB5 3'-UTR SNP (1010A/G), which is located within the microRNA-7 binding site, was correlated with clinical features of bladder cancer.
  
  
  METHODS
  Expression of HOXB5 in 35 human bladder cancer tissues and 8 cell lines were examined using real-time PCR and immunohistochemistry. Next, we explored the biological function of HOXB5 in vitro using cell proliferation, migration and colony formation assays. Using bioinformatics, a SNP (1010A/G) was found located within the microRNA-7 binding site in the 3'-UTR of HOXB5. Real-time PCR was used to test HOXB5 expression affected by different alleles. Finally, multivariate logistic regression analysis was used to determine the relationship between SNP (1010A/G) frequency and clinical features in 391 cases.
  
  
  RESULTS
  HOXB5 was frequently over-expressed both in bladder cancer tissues and cell lines. Inhibition of HOXB5 suppressed the oncogenic function of cancer cells. Next, we demonstrated that a SNP (1010A/G), located within the microRNA-7 binding site in the 3'-UTR of HOXB5, could affect HOXB5 expression in bladder cancer mainly by differential binding activity of microRNA-7 and SNP-related mRNA stability. Finally, we also showed the frequency of 1010G genotype was higher in cancer group compared to normal controls and correlated with the risk of high grade and high stage.
  
  
  CONCLUSIONS
  HOXB5 is overexpressed in bladder cancer. A miRNA-binding SNP (1010A/G) located within 3'-UTR of HOXB5 is associated with gene expression and may be a promising prognostic factor for bladder cancer.
authors: Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
authors: Junhua
authors: J
authors: Luo
authors: Qingqing
authors: Q
authors: Cai
authors: Wei
authors: W
authors: Wang
authors: Hui
authors: H
authors: Huang
authors: Hong
authors: H
authors: Zeng
authors: Wang
authors: W
authors: He
authors: Weixi
authors: W
authors: Deng
authors: Hao
authors: H
authors: Yu
authors: Eddie
authors: E
authors: Chan
authors: Chi-fai
authors: CF
authors: Ng
authors: Jian
authors: J
authors: Huang
authors: Tianxin
authors: T
authors: Lin
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000483:Alleles; D001483:Base Sequence; D001665:Binding Sites; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D002999:Clone Cells; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D020871:RNA Stability / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology
chemical_list: D020413:3' Untranslated Regions; D018398:Homeodomain Proteins; D035683:MicroRNAs; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C489126:HOXB5 protein, human; C549242:MIRN7-1 microRNA, human