TRIM59 regulates autophagy-dependent ferroptosis in non-small cell lung cancer by modulating the ubiquitination of TMEM164.

Abstract

This study investigates the regulatory role of transmembrane protein TMEM164 in ferroptosis and autophagy in non-small cell lung cancer (NSCLC) cells, as well as its interaction with TRIM59. Gene expression analysis was conducted on NSCLC samples, and the effects of TMEM164 knockdown on ferroptosis and autophagy were examined in A549 cells. TMEM164 knockdown in A549 cells reduced ferroptosis by lowering lipid peroxidation and increasing cell viability, suggesting enhanced ferroptosis resistance. TRIM59 promoted ubiquitination and degradation of TMEM164, affecting autophagy and ferroptosis processes. Furthermore, TRIM59 knockdown reversed TMEM164's inhibition of autophagy-dependent ferroptosis, evidenced by changes in Fe2+, MDA, and GSH levels, as well as autophagy and ferroptosis-related protein expressions. Together, TMEM164 and TRIM59 play opposing roles in regulating autophagy and ferroptosis in NSCLC cells. TRIM59 knockdown inhibits the ubiquitination of TMEM164 to induce ferroptosis in NSCLC. This study offers insights for novel NSCLC treatment strategies.