CREB1-driven SRPX upregulation is associated with CD8+ T cell apoptosis and malignant phenotypes in glioblastoma in vitro
Year: 2026
Type: article
Abstract: Background Cytotoxic CD8 + T lymphocytes kill cancer cells and thus contribute to anti-tumor immunity during immunotherapy. Sushi repeat containing protein X-linked (SRPX) is dysregulated in glioblastoma (GBM), but its functional roles remain incompletely understood. Objectives This study aimed to elucidate the functional role of SRPX in mediating malignant phenotypes of GBM cells and promoting CD8⁺ T lymphocyte apoptosis in GBM in vitro . Methods SRPX and cAMP response element binding protein 1 (CREB1) expression were analyzed in human GBM specimens and cell lines. Functional consequences of SRPX manipulation were assessed by cell proliferation, colony formation, migration, and invasion. CD8 + T cells were co-cultured with GBM cells and checked for apoptosis with TUNEL staining. The transcriptional regulation of SRPX by CREB1 was validated through chromatin immunoprecipitation (ChIP) and dual-luciferase assays. Results SRPX mRNA and protein levels were significantly elevated in GBM tumors compared with peritumoral tissues ( p < 0.001). High SRPX expression predicted poor prognosis of GBM patients. SRPX knockdown reduced EdU-positive cells by 36–40%, colony formation by 60–70%, wound closure by 25–30%, and invasive cells by 45–62% across two GBM cell lines (all p < 0.01). SRPX overexpression increased CD8⁺ T cell apoptosis by ∼1.5–2-fold, whereas SRPX silencing decreased it by ∼50% ( p < 0.001). Mechanistically, CREB1 bound to the SRPX promoter ( p < 0.001) and activated its transcription, as confirmed by luciferase assays (∼70% reduction in activity upon CREB1 knockdown, p < 0.01). CREB1 silencing reduced GBM cell proliferation, migration, and invasion, and decreased CD8⁺ T cell apoptosis (all p < 0.001); all these effects were partially reversed upon SRPX re-expression (all p < 0.01). Conclusions Within the limitations of in vitro models, the CREB1/SRPX axis promotes CD8⁺ T cell apoptosis and is associated with enhanced proliferation, migration, and invasion in GBM cell lines. These in vitro findings suggest a candidate immunomodulatory mechanism that warrants further investigation in physiologically relevant models. Importantly, all conclusions are strictly confined to in vitro experimental systems; animal data were withdrawn due to irreproducible quality and are not included, and no in vivo or clinical implications can be drawn from the present study.
Source: Current Proteomics
Institution: Beijing Fengtai Hospital
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W7208804657