J Immunol. 2025 Jun 12:vkaf111. doi: 10.1093/jimmun/vkaf111. Online ahead of print.
ABSTRACT
Colorectal cancer (CRC) progression is closely associated with the dynamic evolution of the tumor microenvironment. As a key component of the tumor microenvironment, tumor-associated neutrophils exhibit protumor properties and dynamically regulate malignant processes by secreting bioactive mediators that coordinate interactions among immune cells. RACGAP1, a cytoplasmic division protein, is highly expressed in various cancers. Here, we investigated the impact of RACGAP1 on CRC cells and the immune microenvironment. Bioinformatics analysis revealed that RACGAP1 was overexpressed in CRC patients. In vitro, Racgap1 silencing triggered G2/M phase arrest and significantly inhibited CRC cell proliferation and induced CRC cell apoptosis. In vivo, Racgap1 knockdown impaired tumor growth in mouse CRC models. RNA sequencing analysis demonstrated that Racgap1 expression significantly influenced immune-related pathways. Further analyses and experimental validation showed that Racgap1 was negatively correlated with neutrophil infiltration in CRC. Chemokine array data indicated that chemokines upregulated following Racgap1 silencing affected neutrophil migration and chemotaxis. Overall, our study suggests that RACGAP1 regulates the CRC microenvironment by modulating tumor cell apoptosis and neutrophil infiltration, highlighting its potential as a biomarker and immunotherapeutic target in CRC.
PMID:40504027 | DOI:10.1093/jimmun/vkaf111