Background: 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 elucidatingits functional mechanisms in glioma progression.
Methods: 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.
Results: SNPH expression was markedlydownregulatedin glioma (P < 0.001), demonstratinghigh diagnostic potential for glioma detection (area under the curve = 0.819). Clinically, decreasedSNPH levelswere associatedwith 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 significantlypredicted worse overall survival (P < 0.001). Functional enrichment analyses revealed SNPH's involvementin 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.
Conclusion: These findings establish SNPH as a novel diagnostic/prognostic biomarker and metastasis suppressor in glioma, functioning through mitochondrial repositioning-mediated inhibition of migration pathways.
The geraniol-derived (seco)iridoid skeleton serves as a fundamental precursor for bioactive monoterpene indole alkaloids (MIAs). Geraniol 8-hydroxylase (G8H), a cytochrome P450 monooxygenase, catalyzes the first committed step of iridoid biosynthesis by hydroxylating geraniol to 8-hydroxygeraniol. This study aims to functionally characterize three homologous CaG8H genes from Camptotheca acuminata and elucidate their distinct roles in iridoid metabolism. Three CaG8H homologs (CaG8H1-3) were identified through phylogenetic and bioinformatic analyses. CaG8H2 was heterologously expressed in Saccharomyces cerevisiae for in vitro enzymatic assays. And in vivo functional verification of the genes using virus-induced gene silencing (VIGS) combined with metabolite quantification by HPLC/GC-MS. Phylogenetic analysis classified CaG8H2 and CaG8H3 as CYP76B subfamily members, while CaG8H1 belongs to CYP76C. Recombinant CaG8H2 specifically converted geraniol to 8-hydroxygeraniol with 23.98 min retention time in GC-MS analysis, whereas CaG8H1 and CaG8H3 showed no detectable activity toward geraniol. VIGS-mediated silencing of CaG8H2 and CaG8H3 reduced their expression by 49% and 57%, respectively, resulting in 41% and 26% decreases in loganic acid and camptothecin accumulation. CaG8H1 silencing had minimal effects on metabolite levels. Among three CYP76 homologs, only CaG8H2 exhibits geraniol 8-hydroxylase activity in vitro, while CaG8H2 and CaG8H3 collectively regulate iridoid biosynthesis in vivo. These findings provide molecular insights into the functional divergence of CYP76 family enzymes and establish a foundation for metabolic engineering of valuable MIAs.
Glioma is a malignant cancer that affects the central nervous system. Early detection of glioma is still difficult due to the hard-to-reach location of the cancer. The use of next generation sequencing is one of the new developments that can be used for diagnosis, however the use of this modality for prognosis is still rarely discussed. This systematic review aims to determine the benefits of using next generation sequencing (NGS) on the assessment of ctDNA or cfDNA concentration, progression free survival (PFS), and overall survival (OS). This systematic review was made using data from six databases, namely PubMed, PMC, ProQuest, Google Schoolar, ScienceDirect, and SCOPUS, and was compiled based on guidelines from PRISMA. Fourteen studies were included in this systematic review with a total of 663 glioma patients. The results of ctDNA measurements generated through the NGS method with liquid biopsy samples show that the higher the grading and sampling when the tumor progresses can increase the ctDNA value. When assessing ctDNA concentrations at baseline when samples were taken, most studies showed a worse prognosis for PFS and OS survival time. However, the grouping of patients in the current studies is still highly variable so further studies with standardized ctDNA cut off values are needed for more precise determination of prognosis.
Background: Non-small cell lung cancer (NSCLC) is a common type of lung cancer with poor prognosis and high mortality in advanced stages. Although secreted phosphoprotein 1 (SPP1) is associated with the progression of NSCLC, its specific mechanisms remain to be explored.
Methods: Through integrated bioinformatics analysis combining weighted gene co-expression network analysis (WGCNA), differential expression analysis, gene enrichment analysis with the Kyoto Encyclopedia of Genes and Genomes (KEGG)/Gene Ontology (GO), and machine learning techniques incorporating database predictions, core genes were identified. Experimental validation was conducted using Western blot, co-immunoprecipitation (Co-IP), cycloheximide (CHX) chase assay, Ubiquitin Immunoprecipitation (Ub-IP), colony formation, flow cytometry, transwell assay, reactive oxygen species (ROS) detection, and quantitative real-time PCR (qRT-PCR). The functional impact of SPP1 on tumor growth was further confirmed through mouse models and immunohistochemistry (IHC).
Results: Based on WGCNA and machine learning, SPP1 was identified as a core gene. SMURF2 ubiquitinated and degraded SPP1. Rescue experiments confirmed that SMURF2 inhibited proliferation and invasion, and promoted apoptosis in NSCLC cells, which were reversed by SPP1 overexpression. Furthermore, SMURF2 enhanced ferroptosis and modulated macrophage polarization via the same ubiquitination mechanism. Animal studies verified that SMURF2-mediated ubiquitination and degradation of SPP1 suppressed tumor growth.
Conclusion: This study aims to investigate the role of SMURF2-mediated ubiquitination of SPP1 in inhibiting malignant progression, promoting ferroptosis, and modulating macrophage polarization in NSCLC, thereby providing a theoretical foundation and new insights for understanding and targeting NSCLC.

