Gomisin B promotes RSL3-induced ferroptosis in neuroblastoma by inhibiting the ESR1/USP7/SREBF1 axis.

IF 5.7 2区医学 Q2 CELL BIOLOGY

Cell Biology and Toxicology Pub Date : 2026-03-09 DOI:10.1007/s10565-026-10155-6

Mengyao Dong, Ting Gao, Yongtao Xu, Qinghao Li, Zhaolong Ma, Bin Zhao, Ming Ming

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引用次数: 0

Abstract

Background: Gomisin B was reported to alleviate neuroblastoma (NB) progression, and the promotion of ferroptosis also inhibited NB. This study aimed to investigate the mechanism by which Gomisin B regulates ESR1 to affect ferroptosis in NB.

Methods: SH-SY5Y and IMR-32 cells were induced to ferroptosis by RSL3 and treated with Gomisin B. Co-IP was utilized to probe the relationship between USP7 and SREBF1. The interaction between ESR1 and USP7 was tested by dual luciferase reporter and ChIP. In addition, cell viability was assessed via CCK-8. Commercial kits were implemented to determine the MDA, GSH, Fe²⁺, and LPO levels. C-11 BODIPY 581/591 fluorescent probe was employed to examine lipid ROS level. BALB/c nude mice were used to construct NB animal models for in vivo studies.

Results: Gomisin B promoted ferroptosis in NB cells and overexpression of ESR1 reversed this phenomenon. Additionally, ESR1 transcriptionally activated USP7 by interacting with the USP7 promoter to inhibit NB cell ferroptosis. USP7 facilitated SREBF1 deubiquitination by binding to SREBF1, thereby enhancing its protein stability. Gomisin B regulated the ESR1/USP7/SREBF1 axis to promote ferroptosis in NB cells. Finally, it was verified at the animal level that Gomisin B promoted ferroptosis and inhibited tumor growth in NB tumor-bearing nude mice.

Conclusion: Gomisin B inhibited the transcriptional activation of USP7 by downregulating ESR1, thereby suppressing the deubiquitination of SREBF1. This enhanced NB ferroptosis to alleviate NB progression.

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Gomisin B通过抑制ESR1/USP7/SREBF1轴促进rsl3诱导的神经母细胞瘤铁凋亡。

背景：据报道，Gomisin B可以缓解神经母细胞瘤（NB）的进展，促进铁下垂也可以抑制NB。本研究旨在探讨Gomisin B调控ESR1影响NB铁下垂的机制。方法：采用RSL3诱导SH-SY5Y和IMR-32细胞凋亡，并用Gomisin b处理，采用Co-IP方法探讨USP7与SREBF1的关系。通过双荧光素酶报告基因和ChIP检测ESR1与USP7的相互作用。此外，通过CCK-8检测细胞活力。采用商业试剂盒测定MDA、GSH、Fe2+和LPO水平。采用C-11 BODIPY 581/591荧光探针检测脂质ROS水平。采用BALB/c裸鼠构建NB动物模型进行体内研究。结果：Gomisin B促进NB细胞铁下垂，而过表达ESR1可逆转这一现象。此外，ESR1通过与USP7启动子相互作用转录激活USP7，抑制NB细胞铁下垂。USP7通过与SREBF1结合促进SREBF1去泛素化，从而增强其蛋白稳定性。Gomisin B调节ESR1/USP7/SREBF1轴，促进NB细胞铁凋亡。最后，在动物水平上验证了Gomisin B在NB荷瘤裸鼠中促进铁下垂，抑制肿瘤生长。结论：Gomisin B通过下调ESR1抑制USP7的转录激活，从而抑制SREBF1的去泛素化。这增强NB铁下垂以减轻NB进展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell Biology and Toxicology 生物-毒理学

CiteScore

9.90

自引率

4.90%

发文量

101

审稿时长

>12 weeks

期刊介绍： Cell Biology and Toxicology (CBT) is an international journal focused on clinical and translational research with an emphasis on molecular and cell biology, genetic and epigenetic heterogeneity, drug discovery and development, and molecular pharmacology and toxicology. CBT has a disease-specific scope prioritizing publications on gene and protein-based regulation, intracellular signaling pathway dysfunction, cell type-specific function, and systems in biomedicine in drug discovery and development. CBT publishes original articles with outstanding, innovative and significant findings, important reviews on recent research advances and issues of high current interest, opinion articles of leading edge science, and rapid communication or reports, on molecular mechanisms and therapies in diseases.