Chronic inflammation with Helicobacter pylori infection is implicated in CD44 overexpression through miR-328 suppression in the gastric mucosa
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...
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Veröffentlicht in: | Journal of gastroenterology 2015-07, Vol.50 (7), p.751-757 |
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Zusammenfassung: | 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. |
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ISSN: | 0944-1174 1435-5922 |
DOI: | 10.1007/s00535-014-1019-y |