(TMEM16F) inhibits gastrointestinal stromal tumor growth and induces ferroptosis.

Herein, we elucidate the potential role of (TMEM16F) in gastrointestinal stromal tumors (GISTs). expression in GIST and adjacent normal tissues was determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. Cell proliferation, apoptosis, and pyroptosis were examined utilizing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, terminal deoxynucleotidyl transferase dUTP Nick-End Labeling staining, and flow cytometry. In addition, the total iron and Fe levels were assessed. IL-18 and IL-1β levels were also evaluated. Lipid reactive oxygen species (ROS), cystine (Cys), glutathione (GSH), and glutathione peroxidase 4 (GPX4) levels were evaluated using appropriate kits. Ferroptotic markers, including , , , and , were analyzed by RT-qPCR, western blotting, and immunohistochemistry. expression decreased in GIST tissues. -plasmid inhibits proliferation, induces apoptosis, and promotes pyroptosis in GIST-T1 and GIST-T1 IR cells. The -plasmid induced ferroptosis, as confirmed by enhanced lipid ROS levels, increased intracellular concentrations of total iron and Fe, promoted and expression, reduced Cys, GSH, and GPX4 levels, and downregulated and expression after and treatment with -plasmid. Moreover, the -plasmid inhibited GIST growth . Therefore, may be a promising therapeutic target for blocking the development of GIST via the induction of apoptosis, pyroptosis, and ferroptosis.