Heat shock protein 27 deficiency promotes ferrous ion absorption and enhances acyl-Coenzyme A synthetase long-chain family member 4 stability to promote glioblastoma cell ferroptosis

Cancer Cell International

Research

Youxin Zhou¹  Guangliang Chen¹  Hao Wang¹  Yue Wu¹  Yongsheng Liu¹  Kai Zhang¹ 

[1] Department of Neurosurgery, Laboratory of Brain and Nerve Research, The First Affiliated Hospital of Soochow University, 215006, Suzhou, Jiangsu, China;

关键词: HSP27;    ACSL4;    GBM;    Fe;    SUMO;    ROS;    Ferroptosis;   

DOI  :  10.1186/s12935-023-02848-3

 received in 2022-10-07, accepted in 2023-01-02,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundGlioblastoma is one of the malignant tumors of the central nervous system with high lethality, high disability and low survival rate. Effective induction of its death is one of the existing challenges. In recent studies, heat shock protein 27 (HSP27) has been shown to be associated with ferroptosis; therefore, targeting HSP27 may be a potential therapeutic approach for GBM.MethodsImmunohistochemistry and western blot analysis were used to detect the expression of HSP27 in GBM tissues. CCK8, plate clone formation assay, EdU proliferation assay for cell proliferation ability, PI, LDH release assay for cell viability. Reactive oxygen, iron levels, and mitochondrial potential for HSP27 silencing were assayed for ferrotosis in vitro. Western blotting and IP were used to verify the relationship between HSP27 and ACSL4. The effect of knockdown of HSP27 on tumor growth capacity was assessed in an intracranial xenograft model.ResultsHSP27 was significantly highly expressed in GBM. In vitro experiments, knockdown of HSP27 significantly induced ferroptosis in GBM cells. IP and western blot demonstrated a sumo-ization link between HSP27 and ACSL4. In vivo experiments, HSP27 deficiency retarded tumor growth rate by promoting ferroptosis.ConclusionsHSP27 deficiency promotes GBM ferroptosis. Targeting HSP27 may serve as a new direction for GBM treatment.

【 授权许可】

CC BY   
© The Author(s) 2023

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