Research progress on molecular mechanism of pyroptosis caused by Helicobacter pylori in gastric cancer

Abstract

Gastric cancer (GC) is a prevalent malignancy worldwide. Helicobacter pylori (H. pylori), a Gram-negative spiral bacterium, has the ability to colonize and persist in the human gastric mucosa. Persistent H. pylori infection has been identified as a major risk factor for ~80% of GC cases. The interplay between H. pylori pathogenicity, genetic background, and environmental factors collectively contribute to GC transformation. Eradicating H. pylori infection is beneficial in reducing the recurrence of gastric cancer and residual cancer. However, the underlying molecular mechanisms involved in GC remain incompletely understood. Additionally, H. pylori reshapes the immune microenvironment within the stomach which may compromise immunotherapy efficacy in infected individuals. Clinical eradication of H. pylori infection still faces numerous challenges. In this review, the authors summarize recent research progress on elucidating the molecular mechanisms underlying H. pylori infection in GC development. Notably, CagA protein-a carcinogenic virulence factor predominantly expressed by Asian strains of H. pylori-induces inflammation and excessive ROS production within gastric mucosa cells. Dysregulation of multiple pyroptosis signalling pathways can lead to malignant transformation of these cells. MiRNA-1290 plays a crucial role in GC initiation and progression while serving as an indicator for disease progression dynamics. Pyroptosis exhibits dual roles both promoting carcinogenesis and inhibiting tumour growth; thus it holds potential clinical applications for drug-resistant GC treatment strategies. Furthermore, pyroptosis may play a regulatory role within the immune system during gastric cancer development. Lastly, the authors provide an overview on current concepts regarding pyroptosis as well as insights into miRNA-1290's pathogenicity and clinical value within immune mechanisms associated with GC, aiming to serve as reference material for researchers.

Keywords: Helicobacter pylori; gastric cancer; miRNA-1290; pyroptosis.

Figure 1

H. pylori promoting pyroptosis and carcinogenesis of gastric mucosal cells. (H. pylori infects gastric mucosal cells, and the virulence factor CagA binds to NOD-like receptors, which are transferred by ASC protein to activate the NLR series of inflammasomes. NLRP activates caspase hydrolase activity, promotes the conversion of cytokines from precursors to mature factors, and activates the N terminus of GSDMD. GSDMD forms holes in the cell membrane and activated cytokines are released. The cytokine storm further damages the gastric mucosa. Under the effect of persistent pyloric infection, mucosal cells undergo carcinogenesis, and immune cells infiltrate into the cancer tissue).

Figure 2

Production and releasing of miRNA-1290 in GC (CagA induces the abnormally high expression of miRNA-1290 in the inflammatory response of H. pylori infection. miRNA-1290 in GC cells forms microvesicles through the cell membrane. The exosomes are released to the extracellular space into the tissue fluid, and then into the peripheral blood circulation system).