LncRNA ALMS1-IT1 modulates ferroptosis and immune evasion in colorectal cancer through activating STAT3.

Colorectal cancer (CRC) represents a significant malignancy within the digestive system, characterized by high incidence and mortality rates. In recent years, molecular targeted therapy has been introduced as a supplementary strategy in CRC management, complementing traditional modalities such as surgery, radiation and chemotherapy. The identification of novel therapeutic targets for CRC remains critically important. Ferroptosis, a unique form of programmed cell death distinct from apoptosis and necrosis, is characterized by cellular damage resulting from iron-induced lipid peroxidation, leading to cell death. This study utilizes a combination of bioinformatics analysis and clinical specimen validation to demonstrate that the long non-coding RNA (lncRNA) ALMS1-IT1 is significantly upregulated in CRC tissues and strongly associated with ferroptosis. Through a series of experimental investigations, we have determined that ALMS1-IT1 negatively regulates ferroptosis in CRC cells, thereby promoting cancer growth and metastasis, acting as an oncogenic factor. Furthermore, we explored the molecular interactions of ALMS1-IT1, revealing its role in activating STAT3 protein phosphorylation. This activation enhances the immune evasion capabilities of CRC cells. Rescue experiments indicated that STAT3 activation is essential for ALMS1-IT1's suppression of ferroptosis, immune evasion and oncogenic behaviour in CRC. Our findings underscore the critical biological role of ALMS1-IT1 in the progression of CRC and suggest its potential as a target for drug development.