Phospholysine Phosphohistidine Inorganic Pyrophosphate Phosphatase Regulates Oxidative Stress Response to Affect the Progression of Gastric Cancer.

[BACKGROUND] Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) has been reported to have anti-carcinogenic effects in gastric cancer, but the specific mechanisms by which LHPP influences GC remain unclear. This study aims to investigate the effect and mechanism of LHPP on GC.

[METHODS] In the in vivo experiments, we constructed a GC mouse model to investigate the impact of LHPP on tumor growth and the expression of related proteins in mice. In the in vitro experiments using human GC cells, we established LHPP overexpression and knockdown cell lines to study the potential mechanisms of LHPP in the progression of GC. We also explored the influence of ROS on the function of LHPP in GC by culturing cells under low glucose and H2O2 conditions.

[RESULTS] In vivo experiments, comparing the tumor development of mice, it was found that LHPP inhibited tumor formation in vivo. Compared with the NC group, it was found that overexpression of LHPP led to a decrease in the expression levels of ROS-related proteins and the protein expression levels of p-Src, p-ERK, and MMP-9 after LHPP overexpression. In vitro experiments, it was found that LHPP overexpression inhibited the migration and invasion of GC cells. However, this regulatory effect of LHPP on GC cells was suppressed when ROS levels increased.

[CONCLUSION] The regulation of oxidative stress response by LHPP is an important mechanism in the development of GC. LHPP inhibits the development of GC by inhibiting the Src-ERK pathway and MMPs. Our study provides a reliable working basis for future in-depth research.