ArticleJournal of translational medicine2025
ZNRF2 is essential for gliomagenesis through orchestrating glycolysis and acts as a promising therapeutic target in glioma.
Article in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Brazilin induces apoptosis and autophagy in human glioblastoma cells via the PI3K/AKT/mTOR signaling pathway.American journal of translational research · 2026Article
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15 authors.
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Abstract
backgroundImproving glioma treatment effectiveness requires a thorough understanding of gliomagenesis. Emerging evidences have proved that zinc and ring finger 2 (ZNRF2) contributes to development of various human malignancies. Nevertheless, a comprehensive study of ZNRF2's role in glioma is absent currently.
methodsUtilizing open resources from Chinese Glioma Genome Atlas (CGGA), Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), Connectivity Map (cMap) and other bioinformatic tools, we systematically examined the expression, clinical significance, prognostic value, regulated biological processes, immune infiltration, and potential inhibitors of ZNRF2 in gliomas. Functional experiments were also performed to validate its oncogenic roles in glioblastoma (GBM) cells.
resultsOur findings revealed that ZNRF2 expression was elevated in gliomas compared to normal brains, and its higher levels were correlated with increased grades and worse patient prognosis. The immune analysis suggested that immunotherapies targeting immune checkpoint genes could be beneficial for glioma patients with elevated ZNRF2 expression. Endogenous ZNRF2 knockdown impaired GBM cell proliferation, G2/M cell cycle progression and glycolysis, which was revealed by reduced ATP, pyruvic acid, lactic acid levels and less glucose uptake. Finally, we identified methylprednisolone (MP) as a potential ZNRF2 inhibitor and validated its anti-glioma effects in vitro. MP also enhanced the sensitization of GBM cells to temozolomide (TMZ), the primary chemotherapeutic agent for GBM in clinic.
conclusionsTaken together, our study demonstrated ZNRF2 as an essential tumor-promoting factor by favoring GBM cell proliferation and glycolysis. Our findings suggested that ZNRF2 might serve as a novel independent prognostic biomarker and promising therapeutic target for glioma patients.
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