Fig. 9.

Schematic diagrams of mechanism diagram and animal experiments.a We collected MGC-803 cells (1 × 10 [7] cells) that were infected by lentivirus with or without PMAN overexpression (six mice per group).Then, suspended in 100 μl serum-free medium and subcutaneously injected and intraperitoneal injected into each flank of 4-week-old BALB/c nude female mice. For the construction of intraperitoneal metastatic orthotopic tumors, we collected MGC-803 cells (5 × 10 [6] cells) that were infected by lentivirus with or without PMAN overexpression (six mice per group).Then, suspended in 40 μl serum-free medium (50% Matrigel) and gastric subserosal injection into each flank of 4-week-old BALB/c nude female mice.b Schematic diagram of PMAN regulating ferroptosis through SLC7A11 during hypoxia. The expression of HIF-1⍺ is up-regulated under hypoxia and as a transcription factor to activates the expression of PMAN by combining with the promoter sequence HRE of PMAN. PMAN directly binds to ELAVL1 and improves the cytoplasmic translocation of ELAVL1. ELAVL1 directly binds to the (GUUU) site of the mRNA of SLC7A11 to improve the stability of mRNA and enhance the expression of SLC7A11. Tumor cells can transport Cys (cystine) into the cell and reduce it to cysteine through the overexpression of SLC7A11, and participate in the synthesis of glutathione (GSH). Reducing the accumulation of ROS and iron in tumor cells and the destruction of mitochondria. Thereby inhibit the occurrence of ferroptosis and promote the growth of tumor cells.