OSBPL3 regulates colorectal cancer progression by modulating gut microbiota and tumor immune microenvironment

This study aimed to explore the biological function of Oxysterol Binding Protein-Like 3 (OSBPL3) in colorectal cancer (CRC) and its correlation with gut microbiota homeostasis, providing insights for individualized CRC prevention and treatment. Using public databases, we analyzed OSBPL3’s role in CRC, validated its prognostic value via clinical data and IHC, and identified its impact on CRC progression through functional assays and an orthotopic model. After in vivo OSBPL3 knockdown, we collected mouse feces, blood, and colorectal tissue, and used multi-omics analyses (16 S rRNA sequencing, metabolomics, transcriptomics) to link OSBPL3 to gut microbiota, metabolic pathways, and differentially expressed genes, locating key microbes which were further verified in vitro and vivo to uncover their immune-related anti-CRC mechanisms. Results showed that OSBPL3 was elevated in CRC tissues and correlated with poor prognosis. OSBPL3 knockdown reduced CRC cell proliferation, migration, and invasion, increased apoptosis, and was accompanied by altered gut microbiota composition, including increased Eubacterium ruminantium and Roseomonas . Administration of these bacteria to mice was associated with increased intratumoral CD8⁺T cell proportion and reduced tumor growth, suggesting their potential association with tumor immune microenvironment remodeling. In conclusion, abnormal OSBPL3 expression was closely associated with gut microbiota dysbiosis and alterations in the tumor immune microenvironment in CRC. Eubacterium ruminantium and Roseomonas may serve as key microbiota associated with OSBPL3-related immune microenvironment remodeling, providing a basis for further mechanistic and therapeutic investigation.