• SNPH is downregulated in glioma and serves as a novel diagnostic biomarker. • Low SNPH expression predicts poor prognosis in glioma patients. • SNPH downregulation is linked to an immunosuppressive glioma microenvironment. • SNPH inhibits invasion/EMT via perinuclear mitochondrial clustering. • Mechanistically, SNPH attenuates focal adhesion maturation and FAK signaling. Glioma remains a lethal brain malignancy with a dismal prognosis. Syntaphilin (SNPH), a mitochondrial anchoring protein, shows emerging relevance in cancer biology. This study investigates the diagnostic and prognostic potential of SNPH, while elucidating its functional mechanisms in glioma progression. The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), Genotype-Tissue Expression (GTEx) and Human Protein Atlas (HPA) were utilized to systematically analyze SNPH, including its differential transcriptional and translational expression, survival correlation, functional enrichment, and immune microenvironment in glioma. Subsequently, the effects of SNPH on cell migration, invasion, mitochondria distribution, epithelial-mesenchymal transition, focal adhesion (FA) maturation and FA kinase (FAK) signaling were validated via in vitro. SNPH expression was markedly downregulated in glioma (P < 0.001), demonstrating high diagnostic potential for glioma detection (area under the curve = 0.819). Clinically, decreased SNPH levels were associated with aggressive features (WHO grade G4, glioblastoma subtype) (both P < 0.001), unfavorable molecular characteristics IDH-wildtype (P = 0.005), 1p19q non-codeletion (P < 0.001), and significantly predicted worse overall survival (P < 0.001). Functional enrichment analyses revealed SNPH’s involvement in immunomodulation and migration-related processes, particularly FA pathway and FAK signaling. Immune profiling indicated an inverse correlation between SNPH expression and the abundance of T helper cells, macrophages and neutrophils. In vitro, SNPH overexpression suppressed invasion and epithelial-mesenchymal transition. Mechanistically, it promoted perinuclear mitochondrial clustering, attenuated FA maturation, FAK phosphorylation and RhoA/Rac1/Cdc42 expression. These findings establish SNPH as a novel diagnostic/prognostic biomarker and metastasis suppressor in glioma, functioning through mitochondrial repositioning-mediated inhibition of migration pathways.
Tian et al. (Sun,) studied this question.