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Published on: September 1, 2010
Establishment and transcriptomic characteristics of radio-resistant meningioma cell lines
Jinxiu Yu1,2,3, Leihao Ren1,2,3, Tianqi Wu1,2,3
1Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, No. 12 Middle Wulumuqi Road, Jingan District, Shanghai, 200040, China.
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.
Insights
Radio-resistant meningioma cells show increased survival and DNA repair. Thymidine kinase 1 (TK1) was identified as a key gene, serving as a potential biomarker and therapeutic target for improving meningioma radio-resistance.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Radio-resistance is a major obstacle in treating meningioma, a common primary brain tumor.
- Understanding the molecular mechanisms of radio-resistance is crucial for developing effective therapeutic strategies.
Purpose of the Study:
- To establish radio-resistant meningioma cell lines.
- To investigate the molecular underpinnings of radio-resistance in meningioma.
- To identify potential biomarkers and therapeutic targets for overcoming radio-resistance.
Main Methods:
- Development of radio-resistant meningioma cell lines (IOMM-Lee-RR, CH157-RR) via progressive radiation.
- Assessment of cellular characteristics including morphology, radiosensitivity, apoptosis, viability, migration, invasion, cell cycle, and DNA repair.
- Transcriptome sequencing, KEGG and GO enrichment analyses, and protein-protein interaction (PPI) analysis to identify key genes.
- Validation of Thymidine kinase 1 (TK1) expression in clinical meningioma samples and datasets.
Main Results:
- Radio-resistant cells demonstrated enhanced survival, reduced apoptosis, increased viability, migration, and invasion.
- These cells exhibited altered cell cycle dynamics (G0/G1 accumulation) and improved DNA repair capacity.
- Transcriptome analysis highlighted enrichment in metabolic pathways, DNA repair, and cell cycle regulation.
- Thymidine kinase 1 (TK1) was identified as a crucial hub gene, highly expressed in recurrent/high-grade meningiomas and linked to poor prognosis.
Conclusions:
- Radio-resistant meningioma cells possess enhanced DNA repair, migratory, invasive, and altered cell cycle capabilities.
- Thymidine kinase 1 (TK1) is a promising biomarker for predicting meningioma radio-resistance and recurrence.
- Targeting TK1 may represent a novel therapeutic strategy to overcome radio-resistance in meningioma treatment.
