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Updated: Sep 17, 2025

Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
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Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics

Published on: March 15, 2024

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CircMAN1A2 Levels Determine GBM Susceptibility to TMZ in a Pathway Involving TEP1- and KEAP1-Mediated NRF2

Xinqiao Li1, Jinpeng Hu1, Wei Zheng2

  • 1Department of Neurosurgery, The First Hospital of China Medical University, Heping District, Shenyang, China.

CNS Neuroscience & Therapeutics
|June 30, 2025
PubMed
Abstract

Insights

Circular RNA MAN1A2 (circMAN1A2) suppresses glioblastoma growth and temozolomide (TMZ) resistance by inducing ferroptosis. This finding highlights circMAN1A2 as a potential therapeutic target for glioblastoma treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Glioblastoma (GBM) is an aggressive brain tumor with poor prognosis and resistance to temozolomide (TMZ).
  • The role of downregulated circular RNAs (circRNAs) in GBM progression is not well understood.

Purpose of the Study:

  • To investigate the role of circMAN1A2 in glioblastoma (GBM) progression and temozolomide (TMZ) resistance.
  • To elucidate the underlying molecular mechanisms of circMAN1A2's function in GBM.

Main Methods:

  • CircRNA sequencing and analysis of public datasets to identify dysregulated circRNAs in GBM.
  • Functional assays in patient-derived glioma stem-like cells (GSCs) with circMAN1A2 manipulation.
  • In vivo mouse models to assess therapeutic effects.

Main Results:

  • CircMAN1A2 was significantly downregulated in GBM and correlated with poorer survival.
  • Overexpression of circMAN1A2 inhibited GSC proliferation, stemness, invasion, and reversed TMZ resistance by inducing ferroptosis.
  • CircMAN1A2 modulated the TEP1-KEAP1-NRF2-ANXA1 axis, impacting NRF2 degradation and tumor-associated macrophage (TAM) polarization.

Conclusions:

  • CircMAN1A2 suppresses GBM progression and TMZ resistance through ferroptosis induction and regulation of the TEP1-KEAP1-NRF2-ANXA1 pathway.
  • CircMAN1A2 represents a promising therapeutic target for glioblastoma.
Keywords:
ANXA1KEAP1‐NRF2 pathwaycircRNAglioma stem cellstumor‐associated macrophages

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