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circNEIL3 Stabilizes SPI1 mRNA and Promotes Glioma Progression and Temozolomide Resistance by Binding to U2AF2

Zhi Xue1, Qian Peng2, Zhonghao Liu1

  • 1Department of Neurosurgery, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha City, China.

Molecular Cancer Research : MCR
|December 18, 2025
PubMed

Insights

Circular RNA circNEIL3 promotes glioma progression and temozolomide (TMZ) resistance by stabilizing SPI1 mRNA via U2AF2 interaction. Inhibiting circNEIL3 enhances glioma cell sensitivity to TMZ, offering a potential therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Temozolomide (TMZ) resistance is a significant challenge in glioma treatment.
  • Circular RNA circNEIL3 is implicated in glioma progression, but its role in TMZ resistance is unknown.

Purpose of the Study:

  • To investigate the function of circNEIL3 in glioma development and its association with TMZ resistance.
  • To elucidate the molecular mechanism by which circNEIL3 influences TMZ resistance in glioma.

Main Methods:

  • Quantitative real-time PCR and Western blotting to assess circNEIL3, U2AF2, and SPI1 expression.
  • Cellular assays (proliferation, apoptosis) and in vivo mouse models to evaluate the impact of circNEIL3 inhibition.
  • RNA immunoprecipitation (RIP) assays to confirm interactions between circNEIL3, U2AF2, and SPI1 mRNA.

Main Results:

  • circNEIL3 is overexpressed in glioma tissues and cells, correlating with TMZ resistance.
  • Inhibition of circNEIL3 increased glioma cell sensitivity to TMZ.
  • circNEIL3 interacts with U2AF2 and SPI1 mRNA, stabilizing SPI1 expression and promoting glioma malignancy.
  • SPI1 silencing partially reversed the effects of circNEIL3 on glioma cell proliferation and apoptosis.

Conclusions:

  • circNEIL3 promotes glioma progression and TMZ resistance by stabilizing SPI1 mRNA through the U2AF2 complex.
  • The circNEIL3/U2AF2/SPI1 axis is a novel therapeutic target for overcoming TMZ resistance in gliomas.

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