MYLK-AS1 Enhances Glutamine Metabolism to Promote EGFR Inhibitor Resistance in Non-Small Cell Lung Cancer

Here we identified a role for the lncRNA MYLK-AS1 promoting acquired TKI resistance of lung cancer in vitro and in vivo. MYLK-AS1 bound and directly drove phase separation of interleukin enhancer binding factor 3 (ILF3), thus interacting with the 3'UTR of glutamate dehydrogenase 1 (GLUD1) to post-transcriptionally promote its mRNA stability, thus enhancing mitochondrial glutamine catabolism, promoting TKI resistance. The MYLK-AS1/ILF3/GLUD1 may be a target for overcoming TKI resistance in lung cancer. Overall design: RNA-seq analysis was performed after knockdown of MYLK-AS1 in PC9/GR cell line.