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Updated: Aug 4, 2025
The Clinical Application of Tumor Treating Fields Therapy in Glioblastoma
Published on: April 16, 2019
SRSF4 Confers Temozolomide Resistance of Glioma via Accelerating Double Strand Break Repair
Yi Sun1, Xingdong Liu1, Zhiqiang Wu1
1Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China.
Abstract:
Temozolomide (TMZ)-based chemotherapy plays a central part in glioma treatment. However, prominent resistance to TMZ is a major change by now. In this study, expression and prognosis of SRSF4 were analyzed using multiple public datasets. Therapeutic efficacy against TMZ resistance was determined by assessing colony formation, flow cytometry, and western blot assays. Bio-informational analysis, immunofluorescence (IF), and western blot assays were performed to evaluate double strand break repair. An orthotopic xenograft model was used to exam the functional role of SRSF4. Here, we found that SRSF4 expression was associated with histological grade, IDH1 status, 1p/19q codeletion, molecular subtype, tumor recurrence, and poor prognosis. SRSF4 promotes TMZ resistance through positively regulating MDC1, thereby accelerating double strand break repair. Targeting SRSF4 could significantly improve chemosensitivity. Taken together, our collective findings highlight an important role of SRSF4 in the regulation of TMZ resistance by modulation of double strand break repair.
Insights
SRSF4 promotes resistance to temozolomide (TMZ) chemotherapy in glioma by enhancing DNA repair. Targeting SRSF4 could improve treatment effectiveness for patients with glioma.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Temozolomide (TMZ) chemotherapy is a cornerstone in glioma treatment.
- Acquired resistance to TMZ significantly limits its therapeutic efficacy.
- Understanding the mechanisms underlying TMZ resistance is crucial for improving patient outcomes.
Purpose of the Study:
- To investigate the role of SRSF4 in temozolomide (TMZ) resistance in glioma.
- To elucidate the mechanism by which SRSF4 influences TMZ resistance.
- To evaluate the therapeutic potential of targeting SRSF4 in overcoming TMZ resistance.
Main Methods:
- Analysis of SRSF4 expression using public datasets.
- Assessment of therapeutic efficacy against TMZ resistance via colony formation, flow cytometry, and Western blot.
- Evaluation of DNA double-strand break repair using bioinformatic analysis, immunofluorescence, and Western blot.
- Functional assessment of SRSF4 using an orthotopic xenograft model.
Main Results:
- SRSF4 expression correlates with glioma histological grade, IDH1 status, 1p/19q codeletion, molecular subtype, tumor recurrence, and poor prognosis.
- SRSF4 promotes TMZ resistance by positively regulating MDC1, which accelerates double-strand break repair.
- Targeting SRSF4 significantly enhances chemosensitivity in preclinical models.
Conclusions:
- SRSF4 plays a critical role in regulating temozolomide (TMZ) resistance in glioma.
- SRSF4 mediates TMZ resistance through the modulation of DNA double-strand break repair.
- Inhibition of SRSF4 represents a promising therapeutic strategy to overcome TMZ resistance in glioma patients.
