P2RX1 in neutrophils mediates JAK/STAT signaling pathway to regulate malignant phenotype of gastric Cancer cells.

Abstract

Gastric cancer is one of the most frequent malignancies and a serious concern in the global public health realm. Neutrophils, the most numerous myeloid cells in human blood, are emerging as significant regulatory variables in cancer. This study examines the molecular processes behind the link between gastric cancer's malignant character and neutrophils in the disease. This study aims to reveal the role of P2RX1 in neutrophils in gastric cancer and investigate its effects on the migration, invasion, and apoptosis of gastric cancer cells, with the hope of providing new targets and strategies for the treatment of gastric cancer. P2RX1 expression levels in gastric cancer samples were examined using The Cancer Genome Atlas-Stomach adenocarcinoma (TCGA-STAD). The signal pathways enriched by P2RX1-related differential gene expression were examined using GSEA. P2RX1 mRNA levels were examined using qPCR. Jak/Stat signaling pathway-related proteins and P2RX1 expression levels were subjected to western blot analysis. The apoptotic rate, migration, invasion, and cell viability were evaluated using flow cytometry, Transwell, and CCK-8 tests. Immunohistochemistry was used to detect the expression of P2RX1 in tumor tissues. Neutrophils and P2RX1 were both underexpressed in gastric cancer. In gastric cancer neutrophils, overexpression of P2RX1 increased cancer cell apoptosis while suppressing migration, invasion, and viability of the cells. Jak/Stat signaling pathway was connected to production of neutrophil P2RX1, and P2RX1 overexpression could trigger the pathway in vivo and in vitro. By activating its own Jak/Stat signaling pathway, overexpression of P2RX1 in gastric cancer neutrophils improved neutrophil survival, which in turn suppressed the migration, invasion, and viability of gastric cancer cells and raised their apoptosis rate. This suggests that P2RX1 may play a significant anti-tumor role in the tumor microenvironment of gastric cancer, indicating its value as a potential therapeutic target.