Downregulation of lncRNA MNX1-AS1 promotes the ferroptosis and apoptosis of non-small cell lung cancer

Non-small cell lung cancer (NSCLC), the main histological type of lung cancer, poses a serious threat to human health. Increasing evidence has shown that long non-coding RNA (lncRNA) MNX1-AS1 is involved in the development and progression of cancers, including lung cancer. Apoptosis and ferroptosis, which are two forms of regulated cell death, can be induced by anti-cancer drugs. However, the roles of MNX1-AS1 in apoptosis and ferroptosis are still unclear. Here, we found that knockdown of MNX1-AS1 promoted the ferroptosis induced by RSL3 in NSCLC cells, with a decrease in cell viability and increases in reactive oxygen species (ROS) and malondialdehyde (MDA) levels. Meanwhile, acridine orange/ethidium bromide (AO/EB) double staining, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay and Annexin V/PI double staining revealed that knockdown of MNX1-AS1 promoted the apoptosis caused by paclitaxel in NSCLC cells. In addition, knockdown of MNX1-AS1 resulted in increased expression of pro-apoptotic protein BAX as well as the cleaved caspase-3 and PARP1, and decreased expression of anti-apoptotic protein Bcl-2. RNA sequencing and quantitative real-time PCR assay identified that the expression of ACSL4 was increased, while the expression of ABCG2 was reduced when MNX1-AS1 was knocked down. Rescue assay showed that ACSL4 and ABCG2 were involved in MNX1-AS1-mediated ferroptosis and apoptosis, respectively. Furthermore, knockdown of MNX1-AS1 increased the sensitivity of NSCLC cells to the combination of RSL3 and paclitaxel. Taken together, our data suggest that MNX1-AS1 might be a potential therapeutic target for lung cancer, especially in combination of ferroptosis and/or apoptosis-inducing drugs.