CIITA was involved in regulating ACSL4-dependent ferroptosis in gastric cancer cells.

In this study, we discussed the impact of CIITA on the occurrence and development of gastric cancer, as well as its potential mechanisms. In this study, N87-C and AGS were used as in vitro research subjects. After knocking down and overexpressing CIITA, CCK8, ELISA, reactive oxygen species (ROS), JC-1, immunofluorescence and western blot were used to assess the effect of CIITA on ferroptosis. To further validate the potential mechanism of CIITA, we continued to transfect lentiviruses cloned with ACSL4 knockdown into cells and repeated the above experiment. In addition, we constructed a subcutaneous transplant tumor model to validate the results of in vitro experiments. In vitro experiments showed that overexpressed CIITA promoted ferroptosis in gastric cancer cells, manifested as the decreased cell viability, increased ROS production, decreased mitochondrial membrane potential, and changes in the expression of ferroptosis-related proteins and secreted factors. After knocking down CIITA, the above results were reversed, inhibiting ferroptosis. In addition, we confirmed that the effect of CIITA on ferroptosis was related to ACSL4. In vitro experiments also confirmed that CIITA overexpression promoted ferroptosis and inhibited tumor growth, while low CIITA had the opposite effect. Overexpressed CIITA promoted ferroptosis and inhibited gastric cancer growth by upregulating ACSL4. CIITA may be a potential therapeutic target for gastric cancer and may have certain predictive value in future clinical applications.