title: Helicobacter pylori induces promoter hypermethylation and downregulates gene expression of IRX1 transcription factor on human gastric mucosa.
abstract: OBJECTIVE
  Gene silence of IRX1 tumor suppressor by promoter CpG methylation combined with loss of heterozygosity (LOH) has been identified in human gastric cancer. This study investigated the association between methylation of IRX1 and Helicobacter pylori infection in gastric mucosa tissues and cell line.
  
  
  METHODS
  IRX1 methylation was studied by methylation specific polymerase chain reaction (MSP) and bisulfate sequencing polymerase chain reaction (BSP) methods in gastric mucosa tissues from H. pylori-positive chronic gastritis patients or H. pylori-negative chronic gastritis patients. Promoter activity, methylation status and gene expressing level of IRX1 were evaluated by persistent infecting H. pylori on human gastric cells GES-1 in vitro. Electron microscopy was used to observe the effect of H. pylori infection on GES-1 gastric mucosa cells.
  
  
  RESULTS
  The methylation level of IRX1 promoter in H. pylori positive chronic gastritis and H. pylori negative chronic gastritis was 55.30%±13.17 versus 5.20%±6.31, respectively (P<0.01). H. pylori infection stimulated increased microvillus, and mucous secretion on GES-1 cells. Infection of H. pylori induced IRX1 promoter methylation and downregulation of the promoter activity as well as gene expression significantly.
  
  
  CONCLUSIONS
  This study firstly demonstrated that H. pylori infection contributes to IRX1 promoter methylation on gastric mucosa.
authors.affiliation: Department of Surgery of Shanghai Ruijin Hospital and Shanghai Institute of Digestive Surgery, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Xiao Bo
authors.initials: XB
authors.lastname: Guo
authors.forename: Lei
authors.initials: L
authors.lastname: Guo
authors.forename: Qiao Ming
authors.initials: QM
authors.lastname: Zhi
authors.forename: Jun
authors.initials: J
authors.lastname: Ji
authors.forename: Jin Ling
authors.initials: JL
authors.lastname: Jiang
authors.forename: Rong Juan
authors.initials: RJ
authors.lastname: Zhang
authors.forename: Jia Nian
authors.initials: JN
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Xue Hua
authors.initials: XH
authors.lastname: Chen
authors.forename: Qu
authors.initials: Q
authors.lastname: Cai
authors.forename: Jian Fang
authors.initials: JF
authors.lastname: Li
authors.forename: Min
authors.initials: M
authors.lastname: Yan
authors.forename: Qin Long
authors.initials: QL
authors.lastname: Gu
authors.forename: Bing Ya
authors.initials: BY
authors.lastname: Liu
authors.forename: Zheng Gang
authors.initials: ZG
authors.lastname: Zhu
authors.forename: Ying Yan
authors.initials: YY
authors.lastname: Yu
mesh_terms: D016022:Case-Control Studies; D002460:Cell Line; D002908:Chronic Disease; D019175:DNA Methylation; D015536:Down-Regulation; D005753:Gastric Mucosa / Q000378:metabolism / Q000382:microbiology* / Q000648:ultrastructure; D005756:Gastritis / Q000235:genetics / Q000378:metabolism / Q000382:microbiology*; D017930:Genes, Reporter; D016481:Helicobacter Infections / Q000235:genetics / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D016480:Helicobacter pylori / Q000472:pathogenicity*; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
chemical_list: D018398:Homeodomain Proteins; C501591:IRX1 protein, human; D014157:Transcription Factors