Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China.
Department of Neurosurgery, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, Jiangsu, China.
J Mol Neurosci. 2023 May;73(4-5):259-268. doi: 10.1007/s12031-023-02115-0. Epub 2023 Apr 4.
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.
替莫唑胺（TMZ）为基础的化疗在神经胶质瘤的治疗中起着核心作用。然而，目前 TMZ 显著耐药是一个重大变化。在这项研究中，我们使用多个公共数据集分析了 SRSF4 的表达和预后。通过评估集落形成、流式细胞术和 Western blot 分析来确定对 TMZ 耐药的治疗效果。通过生物信息学分析、免疫荧光（IF）和 Western blot 分析来评估双链断裂修复。使用原位异种移植模型来检验 SRSF4 的功能作用。在这里，我们发现 SRSF4 的表达与组织学分级、IDH1 状态、1p/19q 共缺失、分子亚型、肿瘤复发和预后不良有关。SRSF4 通过正向调节 MDC1 促进 TMZ 耐药，从而加速双链断裂修复。靶向 SRSF4 可显著提高化疗敏感性。总之，我们的研究结果强调了 SRSF4 在通过调节双链断裂修复来调控 TMZ 耐药中的重要作用。
