title: Rs56288038 (C/G) in 3'UTR of IRF-1 Regulated by MiR-502-5p Promotes Gastric Cancer Development.
abstract: OBJECTIVE
  Interferon regulatory factor 1 (IRF-1) has been shown to function as a transcriptional activator or repressor of a variety of target genes. However, its upstream, non-coding RNA-related regulatory capacity remains unknown. In this study, we focus on the miRNA-associated single nucleotide polymorphisms (SNPs) in the 3'untranslated region (UTR) of IRF-1 to further investigate the functional relationship and potential diagnostic value of the SNPs and miRNAs among Chinese gastric cancer (GC) patients.
  
  
  METHODS
  We performed a case-control study with 819 GC patients and 756 cancer-free controls. Genotyping by realtime PCR assay, cell transfection, and the dual luciferase reporter assay were used in our study, and the 5-year overall survival rate and relapse-free survival rate in different groups were investigated.
  
  
  RESULTS
  We found that patients suffering from Helicobacter pylori (Hp) infection were the susceptible population compared to controls. SNP rs56288038 (C/G) in IRF-1 3'UTR was involved in the occurrence of GC by acting as a tumor promoter factor. SNP rs56288038 (C/G) could be up-regulated by miR-502-5p, which caused a down-regulation of IRF-1 in cell lines and decreased apoptosis induced by IFN-γ. Carrying the G genotype was related to significantly low expression of IRF-1 and Hp infection, poor differentiation, big tumor size, invasion depth, as well as the high probability of metastasis, and moreover, the C/G SNP was associated with shorter survival of GC patients with five years of follow-up study.
  
  
  CONCLUSIONS
  our findings have shown that the SNP rs56288038 (C/G) in IRF-1 3'UTR acted as a promotion factor in GC development through enhancing the regulatory role of miR-502-5p in IRF-1 expression.
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.forename: Huan
authors.initials: H
authors.lastname: Yang
authors.forename: Liqin
authors.initials: L
authors.lastname: Shen
authors.forename: Ji
authors.initials: J
authors.lastname: Wang
authors.forename: Wangyang
authors.initials: W
authors.lastname: Pu
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Chen
authors.forename: Xudong
authors.initials: X
authors.lastname: Shen
authors.forename: Jinxiang
authors.initials: J
authors.lastname: Fu
authors.forename: Zhixiang
authors.initials: Z
authors.lastname: Zhuang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D001483:Base Sequence; D063646:Carcinogenesis / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D014158:Transcription, Genetic
chemical_list: D020413:3' Untranslated Regions; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; C545730:MIRN502 microRNA, human; D035683:MicroRNAs