Zinc moderates circular RNA CircFOXP1 expression in order to regulate ferroptosis during lung adenocarcinoma.

The present study aimed to gain insight into putative anticancer effect of dietary zinc in rat lung cancer model by targeting ferroptosis. Ferroptosis is an emerging type of programmed cell death, which activates oxidative cell death in an iron and lipid peroxides-dependent manner. Targeting ferroptosis is a novel therapeutic approach for cancer therapy. Circular RNAs (circRNAs), as a form of noncoding RNAs with a specific closed circular sequence are emerging as a new field in cancer research. However, the regulatory mechanisms of circRNAs in ferroptosis during lung cancer development are still elusive. In this work, we elucidate the potential prognostic value and the crucial role of circular RNA circFOXP1 in ferroptosis during lung cancer and modulatory potential of zinc. We found that the expression of circFOXP1 was remarkably up-regulated in clinical tumorous tissues compared with adjacent tissues. The knockdown of circFOXP1 suppressed the cell viability of lung cancer cells. The colony formation counts of lung cancer cells were repressed by the depletion of circFOXP1 as well. Moreover, the treatment of zinc, repressed the cell viability of lung cancer cells and the overexpression of circFOXP1 rescued the phenotype. Meanwhile, the levels of malondialdehyde (MDA), iron, and lipid ROS were enhanced post zinc treatment. Collectively, we concluded that circular RNA circFOXP1 is a potential diagnostic biomarker and contributes to malignant progression by repressing ferroptosis of lung cancer cells. Further, zinc be served as a promising therapeutic approach against lung cancer.