Multi-omics analysis and experiments reveal an association between polystyrene microplastics exposure and colorectal cancer progression.

BACKGROUND: Microplastics have emerged as environmental contaminants, yet their potential role in colorectal cancer (CRC) progression remains incompletely understood. We investigated whether polystyrene microplastics (PS-MPs) are associated with tumor-promoting phenotypes and transcriptomic alterations in CRC. METHODS: We integrated transcriptomic analysis, machine learning, public single-cell RNA sequencing datasets, and functional experiments to investigate the biological effects of PS-MPs. CRC-related candidate genes were identified through bioinformatic analyses and experimentally validated using in vitro assays and a subcutaneous mouse model. RNA sequencing of tumor tissues was further performed to characterize transcriptomic alterations associated with PS-MPs exposure. RESULTS: Six hub genes were identified from integrated bioinformatic analyses, and a LASSO-glmBoost diagnostic model achieved excellent performance in both TCGA and GEO cohorts. Functional experiments demonstrated that PS-MPs enhanced CRC cell proliferation, migration, and tumor growth while reducing apoptosis. RNA sequencing suggested polystyrene microplastics exposure might be associated with transcriptomic alterations including the activation of cell-cycle regulation, inflammatory responses, and DNA repair pathways. CONCLUSION: Our findings suggest that PS-MPs promote CRC progression and are associated with transcriptomic alterations and tumor-related biological processes.