2. Academic Validation
  3. Establishment and transcriptomic characteristics of radio-resistant meningioma cell lines

Establishment and transcriptomic characteristics of radio-resistant meningioma cell lines

  • J Neurooncol. 2025 Feb 28. doi: 10.1007/s11060-025-04966-6.
Jinxiu Yu # 1 2 3,  Leihao Ren # 1 2 3,  Tianqi Wu # 1 2 3,  Lingyang Hua # 1 2 3,  Daijun Wang 1 2 3,  Yang Wang 4,  Qing Xie 1 2 3,  Jiaojiao Deng 5 6 7,  Ye Gong 8 9 10 11 12
Affiliations

Affiliations

  • 1 Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, No. 12 Middle Wulumuqi Road, Jingan District, Shanghai, 200040, China.
  • 2 Institute of Neurosurgery, Fudan University, Shanghai, China.
  • 3 Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Fudan University, Shanghai, China.
  • 4 Department of Radiotherapy, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
  • 5 Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, No. 12 Middle Wulumuqi Road, Jingan District, Shanghai, 200040, China. djjewel@163.com.
  • 6 Institute of Neurosurgery, Fudan University, Shanghai, China. djjewel@163.com.
  • 7 Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Fudan University, Shanghai, China. djjewel@163.com.
  • 8 Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, No. 12 Middle Wulumuqi Road, Jingan District, Shanghai, 200040, China. drgongye@163.com.
  • 9 Institute of Neurosurgery, Fudan University, Shanghai, China. drgongye@163.com.
  • 10 Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Fudan University, Shanghai, China. drgongye@163.com.
  • 11 Department of Critical Care Medicine, Shanghai Medical College, Huashan Hospital, Fudan University, Shanghai, China. drgongye@163.com.
  • 12 Department of Neurosurgery, Department of Critical Care Medicine, Shanghai Medical College, Huashan Hospital, Fudan University, No. 12 Middle Wulumuqi Road, Jingan District, Shanghai, 200040, China. drgongye@163.com.
  • # Contributed equally.
PMID: 40019713 DOI: 10.1007/s11060-025-04966-6
Abstract

Purpose: Radio-resistance poses a significant challenge in meningioma treatment. This study aimed to establish radio-resistant meningioma cell lines and uncover molecular mechanisms driving radio-resistance to identify potential biomarkers and therapeutic targets.

Methods: Radio-resistant meningioma cell lines (IOMM-Lee-RR, CH157-RR) were developed using a progressive radiation dose (cumulative 90 Gy). Cell morphology, radiosensitivity, Apoptosis, viability, migration, invasion, cell cycle, and DNA damage repair were analyzed via clonogenic assays, flow cytometry, and Western blotting. Transcriptome Sequencing was performed to identify differentially expressed genes (DEGs), followed by KEGG and GO enrichment analyses. Protein-protein interaction (PPI) analysis was conducted to identify hub genes. TK1 expression was further validated in a cohort of 350 meningiomas and the GSE189672 dataset.

Results: Radio-resistant meningioma cell lines exhibited enhanced survival, reduced Apoptosis, increased cell viability, and superior migratory and invasive abilities compared to parental cells. Under radiation, these cells showed G0/G1 phase accumulation and reduced G2/M phase arrest, along with enhanced DNA repair capacity, as evidenced by lower γ-H2AX expression and fewer DNA damage foci. Transcriptome analysis revealed significant enrichment in metabolic pathways, DNA repair, and cell cycle regulation. Among 34 hub genes identified, TK1 emerged as a key gene, being highly expressed in recurrent and high-grade meningiomas and positively correlated with Ki67. Analysis of the GSE189672 dataset confirmed TK1 as a poor prognostic factor associated with tumor recurrence.

Conclusion: Radio-resistant meningioma cells exhibit enhanced DNA repair, migration, invasion, and altered cell cycle dynamics. TK1 was identified as a promising biomarker and therapeutic target for overcoming radio-resistance in meningiomas.

Keywords

Meningioma; Radio-resistance; Radiotherapy; TK1.

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