ILF3 promotes colorectal cancer cell resistance to ferroptosis by enhancing cysteine uptake and GSH synthesis via stabilizing SLC3A2 mRNA.

ABSTRACT: Ferroptosis, a type of programmed cell death dependent on iron, is characterized by lipid peroxidation of cellular membranes. However, the roles and underlying mechanisms of RNA-binding proteins (RBPs) in modulating ferroptosis in colorectal cancer (CRC) have not been fully explored. In this study, RNA sequencing (RNA-seq) analysis identified ILF3, an RBP, as a crucial regulator of ferroptosis in CRC cells. Our research demonstrated that ILF3 depletion suppressed CRC cell growth and increased sensitivity to ferroptosis. Combined analysis of RNA-seq data and amino acid metabolomics indicated a relationship between ILF3 and glutathione (GSH) synthesis. Further investigation confirmed that ILF3 knockdown reduced GSH synthesis by regulating SLC3A2-mediated cystine uptake. Mechanistically, ILF3

SUBMITTER: Wang S 

PROVIDER: S-EPMC12284142 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature