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.
Keywords: Glioma; SRSF4; Temozolomide resistance.
© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.