MT1JP/miR-103a-3p induce pyroptosis and regulate the tumor immune microenvironment in gastric cancer.

Immune checkpoint blockade (ICB) has made great progress in treating cancer, regulating the tumor immune microenvironment can improve the efficacy of ICB and has become a major focus. Pyroptosis, as a new form of cell death, has been reported in a few diseases to activate cellular immune responses due to the release of inflammatory factors. This may offer a new approach for regulating the tumor immune microenvironment. MT1JP plays an important role in gastric cancer, but its mechanism of pyroptosis and immunity is unclear. Bioinformatics analysis combined with qRT-PCR revealed the expression levels of MT1JP and miR-103a-3p in GC cells and tissues, and their interactions were revealed by dual-luciferase assay and rescue experiment. The effects of MT1JP on GC cell proliferation, invasion, and migration were assessed by CCK-8, EdU, Colony formation, Wound healing, and Transwell. Western blot, IHC, IF, and ELISA were used to assess the effects of MT1JP/miR-103a-3p in GC cell pyroptosis and immunity. MT1JP expression was downregulated and miR-103a-3p was upregulated in GC cells and tissues, the expression of MPDZ was downregulated in AGS and MKN-45. Overexpression of MT1JP inhibited GC cell proliferation, invasion, and migration. MT1JP directly targets and inhibits miR-103a-3p. MT1JP/miR-103a-3p induced the expression of pyroptosis-related proteins (GSDMD, NLRP3, Caspase1) and inflammatory factors (IL-1β, IL-18), activated the immune pathway Sting/IFN-β, and downregulated PD-L1. Based on bioinformatics analysis and preliminary exploration in this study, MPDZ may be a potential downstream target of miR-103a-3p. MT1JP/miR-103a-3p can induce pyroptosis, activate the immune response, and then inhibited the growth of gastric cancer, possibly acting through MPDZ. This explored a new anti-cancer method to regulate the tumor immune microenvironment.