NK92-exo 通过靶向 miR-663a-SLC11A2 轴诱导 A549 细胞铁死亡

NK92-exo were isolated via ultracentrifugation and density-gradient ultracentrifugation and characterized. The changes related to ferroptosis were determined using specific detection kits and transmission electron microscopy (TEM). Predict miR-663a and SLC11A2 associated with ferroptosis in A549 cells through bioinformatics analysis and validated. Lentivirus infection was used to overexpress SLC11A2 in A549 cells, and the expression levels of GPX4, NRF2, and PTGS2 were analyzed.

NK92-exo were successfully isolated and characterized. Co-culturing NK92-exo with A549 cells significantly increased ferroptosis-related changes, such as elevated MDA, ROS, and Fe 2+ levels, decreased GSH level and mitochondrial membrane potential, and observed shrunken mitochondria and mitochondrial rupture. The expression level of miR-663a was significantly downregulated by NK92-exo treatment, resulting in evident upregulation of its potential target SLC11A2 in A549 cells. Additionally, SLC11A2 overexpression significantly enhanced ferroptosis in A549 cells, an effect that was further enhanced by NK92-exo treatment.

NK92-exo decreased intracellular miR-663a abundance and increased SLC11A2 expression, thereby promoting ferroptosis in A549 cells. These findings suggest that NK92-exo may serve as a novel therapeutic bioproduct for lung cancer treatment.