Helicobacter Pylori Promote B7-H1 Expression by Suppressing miR-152 and miR-200b in Gastric Cancer Cells

PLoS One. 2017 Jan 5;12(1):e0168822. doi: 10.1371/journal.pone.0168822. eCollection 2017.

Abstract

The most common cause of gastric cancer is infection with helicobacter pylori (HP), but the associated molecular mechanism is not well understood. In the present study, we found a marked increase in the expression of B7-H1, a member of the B7 co-stimulatory family of molecules that bind to programmed death-1 (PD-1) and play a critical immunoregulatory role in the cell-mediated immune response, in HP-positive gastric cancer tissue. Infection of cultured gastric cancer cells with HP promoted B7-H1 expression and inhibited miR-152 and miR-200b expression. We further demonstrated that these two miRNAs targeted B7-H1 mRNA and suppressed B7-H1 expression in gastric cancer cells. Finally, B7-H1 expression was found to correlate with miR-152 and miR-200b levels in gastric tumor tissues from human patients. Our findings suggest a novel mechanism by which HP infection promotes gastric cancer and also suggest potential targets, i.e., miR-152 and miR-200b, for the prevention and treatment of gastric cancer.

MeSH terms

  • 3' Untranslated Regions / genetics
  • B7-H1 Antigen / genetics
  • B7-H1 Antigen / metabolism*
  • Cell Line, Tumor
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Helicobacter pylori / pathogenicity*
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / microbiology*

Substances

  • 3' Untranslated Regions
  • B7-H1 Antigen
  • MIRN152 microRNA, human
  • MIRN200 microRNA, human
  • MicroRNAs

Grants and funding

This work was supported by National Natural Science Foundation of China (http://www.nsfc.gov.cn/publish/portal1/): No. 81172294, KT, Role in conceptualization, investigation, resources, writing review & editing, visualization, supervision, project administration and funding acquisition; No. 81572413, KT, Role in conceptualization, investigation, resources, writing review & editing, visualization, supervision, project administration and funding acquisition; No. 81402357, EZ, Role in methodology and software.