Jinxiu Yu, Leihao Ren, Tianqi Wu, Lingyang Hua, Daijun Wang, Yang Wang, Qing Xie, Jiaojiao Deng, Ye Gong
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引用次数: 0
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.
期刊介绍：
The Journal of Neuro-Oncology is a multi-disciplinary journal encompassing basic, applied, and clinical investigations in all research areas as they relate to cancer and the central nervous system. It provides a single forum for communication among neurologists, neurosurgeons, radiotherapists, medical oncologists, neuropathologists, neurodiagnosticians, and laboratory-based oncologists conducting relevant research. The Journal of Neuro-Oncology does not seek to isolate the field, but rather to focus the efforts of many disciplines in one publication through a format which pulls together these diverse interests. More than any other field of oncology, cancer of the central nervous system requires multi-disciplinary approaches. To alleviate having to scan dozens of journals of cell biology, pathology, laboratory and clinical endeavours, JNO is a periodical in which current, high-quality, relevant research in all aspects of neuro-oncology may be found.
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