Fig. 5: LncRNAs participate in the regulation of ferroptosis in NSCLC.
From: Targeting lncRNAs in programmed cell death as a therapeutic strategy for non-small cell lung cancer
Ferroptosis is initiated by blockade of the cellular antioxidant defences depending on glutathione (GSH). Cystine/glutamate antiporter system Xc- is responsible for transporting intracellular glutamate to the outside of the cell and transferring extra-cellular cystine into the cell. Subsequently, cystine is converted into cysteine for the biosynthesis of GSH. GPX4 converts GSH into oxidized glutathione (GSSG), concurrent with cytotoxic lipid peroxide (L-OOH) reduced to the corresponding alcohol (L-OH), thus reducing ROS accumulation. Cellular uptake of circulating iron (Fe3+) is mediated by TFR1 and intracellular iron can also be exported by ferroportin (FPN). The iron oxidoreductase six-transmembrane epithelial antigen of the prostate 3 (STEAP3) reduces Fe3+ to Fe2+, the latter is released from the endosome via divalent metal transporter 1 (DMT1) and then delivered into the unstable iron pool, thereby leading to ROS generation. Aberrant accumulation of ROS ultimately results in lipid peroxidation and ferroptosis. Oncogenic lncRNAs (red font, high expression in NSCLC) and tumour-suppressive lncRNAs (blue font, low expression in NSCLC) participate in lung cancer-associated ferroptosis by regulating ferroptosis-related proteins.
