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.
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. pyloriinfection 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. pyloriinfection 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: Neelakandan Muthukumaran; Karl E Miletti-González; Abhilash K Ravindranath; Lorna Rodríguez-Rodríguez Journal: Mol Cancer Res Date: 2006-08 Impact factor: 5.852
Authors: Can Liu; Kevin Kelnar; Bigang Liu; Xin Chen; Tammy Calhoun-Davis; Hangwen Li; Lubna Patrawala; Hong Yan; Collene Jeter; Sofia Honorio; Jason F Wiggins; Andreas G Bader; Randy Fagin; David Brown; Dean G Tang Journal: Nat Med Date: 2011-01-16 Impact factor: 53.440