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Chronic inflammation with Helicobacter pylori infection is implicated in CD44 overexpression through miR-328 suppression in the gastric mucosa

  • Original Article—Alimentary Tract
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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.

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Acknowledgments

This work was supported in part by the Okukubo Memorial Fund for Medical Research at Kumamoto University School of Medicine, the Medical Research Encouragement Prize of the Japan Medical Association, and the Japan Society for the Promotion of Science Grant-in-Aid for Scientific Research (24591912) (given to T.I.).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan

    Takatsugu Ishimoto, Daisuke Izumi, Masayuki Watanabe, Naoya Yoshida, Kosei Hidaka, Keisuke Miyake, Hidetaka Sugihara, Hiroshi Sawayama, Yu Imamura, Masaaki Iwatsuki, Shiro Iwagami, Yoshifumi Baba & Hideo Baba

  2. Department of Cell Pathology, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan

    Hasita Horlad, Yoshihiro Komohara & Motohiro Takeya

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  1. Takatsugu Ishimoto
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Correspondence to Hideo Baba.

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Ishimoto, T., Izumi, D., Watanabe, M. et al. Chronic inflammation with Helicobacter pylori infection is implicated in CD44 overexpression through miR-328 suppression in the gastric mucosa. J Gastroenterol 50, 751–757 (2015). https://doi.org/10.1007/s00535-014-1019-y

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  • DOI: https://doi.org/10.1007/s00535-014-1019-y

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