title: Genetic variation in a microRNA-502 minding site in SET8 gene confers clinical outcome of non-small cell lung cancer in a Chinese population.
abstract: BACKGROUND
  Genetic variants may influence microRNA-target interaction through modulate their binding affinity, creating or destroying miRNA-binding sites. SET8, a member of the SET domain-containing methyltransferase, has been implicated in a variety array of biological processes.
  
  
  METHODS
  Using Taqman assay, we genotyped a polymorphism rs16917496 T>C within the miR-502 binding site in the 3'-untranslated region of the SET8 gene in 576 non-small cell lung cancer (NSCLC) patients. Functions of rs16917496 were investigated using luciferase activity assay and validated by immunostaining.
  
  
  RESULTS
  Log-rank test and cox regression indicated that the CC genotype was associated with a longer survival and a reduced risk of death for NSCLC [58.0 vs. 41.0 months, P = 0.031; hazard ratio = 0.44, 95% confidential interval: 0.26-0.74]. Further stepwise regression analysis suggested rs16917496 was an independently favorable factor for prognosis and the protective effect more prominent in never smokers, patients without diabetes and patients who received chemotherapy. A significant interaction was observed between rs16917496 and smoking status in relation to NSCLC survival (P<0.001). Luciferase activity assay showed a lower expression level for C allele as compared with T allele, and the miR-502 had an effect on modulation of SET8 gene in vitro. The CC genotype was associated with reduced SET8 protein expression based on immunostaining of 192 NSCLC tissue sample (P = 0.007). Lower levels of SET8 were associated with a non-significantly longer survival (55.0 vs. 43.1 months).
  
  
  CONCLUSIONS
  Our data suggested that the rs16917496 T>C located at miR-502 binding site contributes to NSCLC survival by altering SET8 expression through modulating miRNA-target interaction.
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Jiali
authors.initials: J
authors.lastname: Xu
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Yin
authors.forename: Wen
authors.initials: W
authors.lastname: Gao
authors.forename: Lingxiang
authors.initials: L
authors.lastname: Liu
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Yin
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.forename: Yongqian
authors.initials: Y
authors.lastname: Shu
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D001665:Binding Sites; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D002681:China; D005260:Female; D015870:Gene Expression; D014644:Genetic Variation; D005838:Genotype; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D011110:Polymorphism, Genetic; D011379:Prognosis; D012307:Risk Factors
chemical_list: D020413:3' Untranslated Regions; C545730:MIRN502 microRNA, human; D035683:MicroRNAs; D011495:Histone-Lysine N-Methyltransferase; C470730:KMT5A protein, human