Journal
HELICOBACTER
Volume 26, Issue 4, Pages -Publisher
WILEY
DOI: 10.1111/hel.12813
Keywords
dendritic cell; Helicobacter pylori; JAK2‐ STAT3; miR‐ 375
Categories
Funding
- National Natural Science Foundation of China [81971562]
- Key R&D Plan Project of Ningxia Autonomous Region [2020BFG02012]
- Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions
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This study demonstrated that Helicobacter pylori inhibits the expression of miRNA-375 in the stomach, leading to the activation of the JAK2-STAT3 pathway. This pathway promotes the secretion of IL-6, IL-10, and VEGF, resulting in immature differentiation of DCs and the induction of gastric cancer.
Background Recent studies and clinical samples have demonstrated that Helicobacter pylori could induce the downregulation of miR-375 in the stomach and promote gastric carcinogenesis. However, whether the immune cells are affected by Helicobacter pylori due to the downregulation of miR-375 is unclear. Materials and methods In this study, we constructed an overexpression and knockdown of miR-375 and Helicobacter pylori infection cell models in vitro. In addition, the maturity of dendritic cells (DCs) and the expression of IL-6, IL-10, and VEGF at the transcriptional and translational levels were analyzed. Changes in the JAK2-STAT3 signaling pathway were detected. In vivo, the number changes in CD4+ T and CD8+ T cells and the size changes of tumors via models of transplantable subcutaneous tumors were also analyzed. Results A cell model of Helicobacter pylori and gastric cancer was used to identify the expression of miR-375 and the maturity of dendritic cells. This study found that Helicobacter pylori could downregulate miR-375, which regulates the expression of cytokines IL-6, IL-10, and VEGF in the stomach. MiR-375 regulated the expression of cytokines IL-6, IL-10, and VEGF through the JAK2-STAT3 signaling pathway in vitro. In addition, we found that Helicobacter pylori regulates the maturation of dendritic cells through miR-375. These results were further verified in vivo, and miR-375 diminishes tumor size was also demonstrated. This study showed that immature DCs caused a decrease in the number of CD4+ and CD8+ T cells. Conclusions This study demonstrated that Helicobacter pylori can inhibit miRNA-375 expression in the stomach. Downregulated miR-375 activates the JAK2-STAT3 pathway. Activating the JAK2-STAT3 signaling pathway promotes the secretion of IL-6, IL-10, and VEGF, leading to immature differentiation of DCs and induction of gastric cancer.
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