RBMS2 mediates SLC7A11 transcription-translation to regulate ferroptosis in colorectal cancer

The incidence of colorectal cancer (CRC) increases yearly. Ferroptosis, a form of regulated cell death, has gained extensive attention in cancer research. RNA-binding motif single-stranded interacting protein 2 (RBMS2) has been implicated in various cancers, but its role in CRC and its involvement with ferroptosis remains poorly understood. This study explores the involvement of RBMS2 in CRC development and its potential as a therapeutic target. Functional assays, including CCK-8, colony formation, Transwell migration, invasion assays, and EMT-related gene determination, were conducted to evaluate the effects of RBMS2 overexpression and knockdown. Ferroptosis, apoptosis, and autophagy were assessed using specific inhibitors, ferroptosis inducers, and apoptosis and proliferation detection. The interaction between RBMS2 and SLC7A11 was explored during the ferroptosis process. In vivo experiments involved xenograft models in nude mice to observe tumor growth, EMT, and metastasis. Overexpression of RBMS2 inhibited CRC cell proliferation, migration, and epithelial-mesenchymal transition (EMT). Furthermore, RBMS2 promoted ferroptosis by downregulating SLC7A11. Mechanistic studies revealed that RBMS2 destabilizes SLC7A11 at the mRNA level. In vivo, RBMS2 overexpression significantly suppressed tumor growth and lung/liver metastasis. Our findings indicate that RBMS2 inhibits CRC progression by promoting ferroptosis and regulating SLC7A11 mRNA stability. Targeting the RBMS2-SLC7A11 axis could provide a novel therapeutic strategy for CRC.