By integrating transcriptomic data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and a self-established colorectal cancer (CRC) cohort, we have identified that SYT8 is significantly up-regulated in tumors and is predictive of poor prognosis.Single-cell RNA sequencing, immunohistochemistry, and immunofluorescence experiments demonstrate that SYT8 expression is largely confined to tumor cells, predominantly in the nucleus.Functional assays reveal that depletion of SYT8 impairs, while its overexpression enhances, CRC cell proliferation and invasion.Transcriptomic profiling indicates an enrichment of cell-cycle and epithelial-mesenchymal transition (EMT) signatures.Mechanistically, co-immunoprecipitation/mass spectrometry (co-IP/MS) identifies SETD1A as a direct SYT8-interacting partner.The SYT8-SETD1A axis forms a positive-feedback loop that increases H3K4me3 levels and drives the transcription of pro-tumorigenic genes.Immune profiling further indicates that high SYT8 expression correlates with increased regulatory T-cell infiltration, suggesting an immunosuppressive microenvironment and potential resistance to immunotherapy.Collectively, SYT8 promotes CRC progression through the SETD1A/H3K4me3-mediated activation of the cell cycle, induction of EMT, and remodeling of the immune microenvironment.Therefore, SYT8 is established as a prognostic biomarker and serves as a therapeutic target in colorectal cancer.
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Wei et al. (Sun,) studied this question.
www.synapsesocial.com/papers/69c4cc69fdc3bde448917954 — DOI: https://doi.org/10.1016/j.ajpath.2026.03.006
Jinhong Wei
Chuanjie Zhang
Jinyuan Tian
American Journal Of Pathology
Sun Yat-sen University
Sun Yat-sen Memorial Hospital
Guangdong Academy of Medical Sciences
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