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.