title: Chronic inflammation with Helicobacter pylori infection is implicated in CD44 overexpression through miR-328 suppression in the gastric mucosa.
abstract: BACKGROUND
  Infection with Helicobacter pylori is the main risk factor for development of gastric cancer. CD44 overexpression, especially that of variant 9 (CD44v9), has also been implicated in the local inflammatory response and metaplasia-carcinoma sequence in human stomach. We recently identified miR-328 as one of the microRNAs targeting CD44 in gastric cancer. The aim of the current study was to determine the relationship between miR-328 and CD44v9 expression in H. pylori-infected gastric mucosa during the development of preneoplastic lesions.
  
  
  METHODS
  Immunohistochemical staining of myeloperoxidase and CD44v9 was performed using paraffin-embedded tissue sections obtained from 54 patients who underwent gastric resection without preoperative treatment. The levels of miR-328 expression in the gastric mucosa were measured in the same patients using quantitative reverse transcription polymerase chain reaction.
  
  
  RESULTS
  Both infiltration of myeloperoxidase-positive inflammatory cells and expression of proinflammatory cytokines closely correlated with H. pylori infection in the cancer-afflicted gastric mucosa. High CD44v9 expression levels, identified in the gastric mucosa in 61 % of samples (33/54), correlated significantly with H. pylori infection in the gastric mucosa. Notably, high CD44v9 expression was significantly associated with low miR-328 expression, whereas low CD44v9 expression was significantly associated with high miR-328 expression.
  
  
  CONCLUSIONS
  We showed that miR-328 downregulation and de novo expression of CD44v9 occurred in H. pylori-infected gastric mucosa adjacent to gastric cancer compared with gastric mucosa not infected with H. pylori adjacent to gastric cancer. CD44v9-overexpressing cells are known to acquire reactive oxygen species resistance; thus, these cells may avoid cell death caused by various stress inducers, which may be linked to the origin of gastric cancer development.
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
authors.forename: Takatsugu
authors.initials: T
authors.lastname: Ishimoto
authors.forename: Daisuke
authors.initials: D
authors.lastname: Izumi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Watanabe
authors.forename: Naoya
authors.initials: N
authors.lastname: Yoshida
authors.forename: Kosei
authors.initials: K
authors.lastname: Hidaka
authors.forename: Keisuke
authors.initials: K
authors.lastname: Miyake
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Sugihara
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sawayama
authors.forename: Yu
authors.initials: Y
authors.lastname: Imamura
authors.forename: Masaaki
authors.initials: M
authors.lastname: Iwatsuki
authors.forename: Shiro
authors.initials: S
authors.lastname: Iwagami
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Baba
authors.forename: Hasita
authors.initials: H
authors.lastname: Horlad
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Komohara
authors.forename: Motohiro
authors.initials: M
authors.lastname: Takeya
authors.forename: Hideo
authors.initials: H
authors.lastname: Baba
mesh_terms: D045744:Cell Line, Tumor; D005753:Gastric Mucosa / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D016481:Helicobacter Infections / Q000150:complications* / Q000378:metabolism / Q000382:microbiology; D016480:Helicobacter pylori / Q000302:isolation & purification; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis / Q000235:genetics*; D007150:Immunohistochemistry; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D012334:RNA, Neoplasm / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000209:etiology / Q000235:genetics* / Q000378:metabolism
chemical_list: C497483:CD44 protein, human; D018960:Hyaluronan Receptors; C548170:MIRN328 microRNA, human; D035683:MicroRNAs; D012334:RNA, Neoplasm