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Helicobacter pylori induces promoter hypermethylation and downregulates gene expression of IRX1 transcription factor on human gastric mucosa

Authors

  • Xiao Bo Guo,

    1. Department of Surgery of Shanghai Ruijin Hospital and Shanghai Institute of Digestive Surgery, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
    2. Department of Gastrointestinal Surgery, Provincial Hospital of Shandong University, Jinan, China
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  • Lei Guo,

    1. Department of Surgery of Shanghai Ruijin Hospital and Shanghai Institute of Digestive Surgery, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
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  • Qiao Ming Zhi,

    1. Department of Surgery of Shanghai Ruijin Hospital and Shanghai Institute of Digestive Surgery, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
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  • Jun Ji,

    1. Department of Surgery of Shanghai Ruijin Hospital and Shanghai Institute of Digestive Surgery, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
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  • Jin Ling Jiang,

    1. Department of Surgery of Shanghai Ruijin Hospital and Shanghai Institute of Digestive Surgery, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
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  • Rong Juan Zhang,

    1. Department of Surgery of Shanghai Ruijin Hospital and Shanghai Institute of Digestive Surgery, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
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  • Jia Nian Zhang,

    1. Department of Surgery of Shanghai Ruijin Hospital and Shanghai Institute of Digestive Surgery, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
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  • Jun Zhang,

    1. Department of Surgery of Shanghai Ruijin Hospital and Shanghai Institute of Digestive Surgery, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
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  • Xue Hua Chen,

    1. Department of Surgery of Shanghai Ruijin Hospital and Shanghai Institute of Digestive Surgery, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
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  • Qu Cai,

    1. Department of Surgery of Shanghai Ruijin Hospital and Shanghai Institute of Digestive Surgery, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
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  • Jian Fang Li,

    1. Department of Surgery of Shanghai Ruijin Hospital and Shanghai Institute of Digestive Surgery, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
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  • Min Yan,

    1. Department of Surgery of Shanghai Ruijin Hospital and Shanghai Institute of Digestive Surgery, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
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  • Qin Long Gu,

    1. Department of Surgery of Shanghai Ruijin Hospital and Shanghai Institute of Digestive Surgery, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
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  • Bing Ya Liu,

    1. Department of Surgery of Shanghai Ruijin Hospital and Shanghai Institute of Digestive Surgery, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
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  • Zheng Gang Zhu,

    1. Department of Surgery of Shanghai Ruijin Hospital and Shanghai Institute of Digestive Surgery, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
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  • Ying Yan Yu

    Corresponding author
    1. Department of Surgery of Shanghai Ruijin Hospital and Shanghai Institute of Digestive Surgery, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
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  • A conflict of interest statement: The authors declare that they have no competing financial interests.

Dr Ying Yan Yu, Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Ruijin er Road, no. 197, 200025, Shanghai, China. Email: yingyan3y@yahoo.com.cn

Abstract

Background and Aim:  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.

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