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2000
Volume 25, Issue 11
  • ISSN: 1568-0096
  • E-ISSN: 1873-5576

Abstract

Background

Neuroblastoma (NB) is a well-known pediatric malignancy intertwined with neurodevelopment. Previously implicated in neuronal differentiation, Zinc Finger Protein 536 (ZNF536) has emerged as a promising prognostic and immune-related biomarker in our pan-cancer analysis.

Methods

Single-cell RNA transcriptome sequencing, bulk transcriptome analysis, and immunohistochemistry were used to assess ZNF536 expression and its association with prognosis. Cell proliferation, migration, invasion, and differentiation in ZNF536-knockdown NB cell lines were detected to evaluate the effect of ZNF536 on tumor cells. Vascular Endothelial Growth Factor Receptor 2 (VEGFR2), a potential target of ZNF536, and its downstream PI3K/AKT signaling cascade were investigated using transcriptome sequencing, CUT&Tag, quantitative real-time PCR (qRT-PCR), and Western blotting. The role of ZNF536 in tumorigenesis and the potential regulation axis was evaluated using a BALB/c nude mouse xenograft tumor model.

Results

ZNF536 mRNA and protein expression were significantly higher in NB patients with poor prognosis. , ZNF536 knockdown curtailed proliferation, migration, and invasion of NB cells while fostering differentiation. ZNF536 regulated VEGFR2 expression, thus activating the PI3K-AKT pathway. , ZNF536 knockdown reduced tumor growth and proliferation the VEGFR2-PI3K-AKT pathway.

Conclusion

ZNF536 resulted as a novel prognostic biomarker in NB, promoting oncogenesis through VEGFR2-PI3K-AKT signaling axis modulation, suggesting its therapeutic potential in managing NB progression.

© 2025 Bentham Science Publishers
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2025-12-28

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Zinc Finger Protein 536 is a Potential Prognostic Biomarker that Promotes Neuroblastoma Progression via VEGFR2-PI3K-AKT Pathway
Curr. Cancer Drug Targets< 25, 1447 (2025); https://doi.org/10.2174/0115680096332753240913104409
/content/journals/ccdt/10.2174/0115680096332753240913104409
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  • Article Type:     Research Article
Keyword(s): Neuroblastoma; pediatric oncology; PI3K-AKT signaling; prognostic biomarker; VEGFR2; ZNF536

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