RNPS1 Promotes the Progression of Nonsmall Cell Lung Cancer via ETV4-Mediated Ferroptosis.

Ferroptosis plays a crucial role in regulating tumor growth and represents a promising therapeutic target for nonsmall cell lung cancer (NSCLC). RNA-binding protein with serine-rich domain 1 (RNPS1) has been closely associated with the development of various cancer types, but its role in NSCLC remains unclear. In this study, we used lentiviral vectors to silence or overexpress RNPS1 in NSCLC cells and then assessed cell proliferation along with ferroptosis markers, such as lipid reactive oxygen species (ROS). Bioinformatics analysis revealed that RNPS1 was upregulated in clinical NSCLC samples. Consistently, functional experiments showed that overexpression of RNPS1 promoted cell proliferation, while RNPS1 knockdown inhibited cell proliferation. Furthermore, RNPS1 overexpression attenuated erastin-triggered ferroptosis by suppressing the accumulation of lipid ROS and malondialdehyde, as well as by preventing the depletion of glutathione. Mechanistic investigations identified that RNPS1 stabilized ETS variant transcription factor 4 (ETV4) mRNA. Importantly, blocking ETV4 expression partially reversed RNPS1 overexpression-mediated suppression of ferroptosis. Collectively, these results support the notion that RNPS1 acts as a novel suppressor of ferroptosis in NSCLC progression.