Articles
Vol. 70 No. 1 (2026)
SRSF3 promotes the generation of XBP1s to stabilize autophagy and enhance hypoxia adaptation in glioma
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Published: 3 March 2026
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Hypoxia is a key driver of glioblastoma (GBM) progression. Serine/arginine-rich splicing factor 3 (SRSF3) is associated with the malignant progression of GBM, but its role in the hypoxic microenvironment of GBM remains unclear. This study aimed to explore the regulatory role and molecular mechanisms of SRSF3 in hypoxia adaptation in GBM. The expression of SRSF3 in normal astrocytes and GBM cells was detected. The effects of knockdown or overexpression of SRSF3 combined with hypoxia treatment on malignant phenotypes and hypoxia stress adaptation in GBM cells were evaluated. Cell viability, colony formation, migration, invasion, and cell death assays were performed to assess phenotypic changes. Mechanisms were investigated using mRFP-GFP-LC3, autophagy, and unfolded protein response (UPR)-related molecular detection. SRSF3 was highly expressed in GBM cells. Knockdown of SRSF3 inhibited cell viability, migration, invasion, and colony formation, whereas overexpression of SRSF3 promoted malignant behaviors. Further studies revealed that hypoxia induction significantly increased the expression levels of GRP78, CHOP, ATF4, LC3-II/I, and p62; upregulated the GFP/mRFP ratio; and increased cleaved-caspase3 expression, promoting cell death. Mechanistic studies revealed that SRSF3 overexpression promoted XBP1s formation, alleviated hypoxia-induced autophagic flux blockage, and reduced cell death. The IRE1 RNase inhibitor 4μ8C weakened the SRSF3-mediated promotion of XBP1s generation. SRSF3 enhances adaptive UPR output by promoting IRE1-dependent XBP1 splicing, thereby maintaining autophagic flux and promoting GBM cell survival under hypoxic conditions.
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CRediT authorship contribution
Bohu Liu, Jun Pu, conceptualization. Xiaoran Zhang, Jintao Tian, Zhenghu Xu, formal analysis. Bohu Liu, Xiaobin Huang, data acquisition, methodology, writing-original draft. Jun Pu, funding acquisition, resources, project administration. Xuhui Li, software. Xiaoran Zhang, Jintao Tian, validation. Jinxi Zhao, visualization. Zhenghu Xu, Jun Pu, writing-review and editing. All the authors contributed substantially to this manuscript, read and approved the final manuscript.
Supporting Agencies
National Natural Science Foundation of China , First-Class Discipline Team of Kunming Medical University , Yunnan Fundamental Research Projects, NHC Key Laboratory of Drug Addiction MedicineData Availability Statement
The data are available from the corresponding author on reasonable request.
How to Cite
1.
Liu B, Zhang X, Tian J, Huang X, Li X, Zhao J, et al. SRSF3 promotes the generation of XBP1s to stabilize autophagy and enhance hypoxia adaptation in glioma. Eur J Histochem [Internet]. 2026 Mar. 3 [cited 2026 Apr. 2];70(1). Available from: https://www.ejh.it/ejh/article/view/4530
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