Related Experiment Video
Updated: Mar 11, 2026
Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
Published on: March 15, 2024
Gomisin B promotes RSL3-induced ferroptosis in neuroblastoma by inhibiting the ESR1/USP7/SREBF1 axis
Mengyao Dong1, Ting Gao2, Yongtao Xu2
1Department of Neonatology, The Affiliated Taian City Central Hospital of Qingdao University, Shandong, Taian, 271000, People's Republic of China.
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.
Insights
Gomisin B promotes ferroptosis in neuroblastoma (NB) by downregulating ESR1, inhibiting USP7, and suppressing SREBF1 deubiquitination. This mechanism alleviates NB progression and tumor growth.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Neuroblastoma (NB) progression can be alleviated by promoting ferroptosis.
- Gomisin B has shown potential in inhibiting NB progression.
Purpose of the Study:
- To investigate the mechanism of Gomisin B in regulating ESR1 and affecting ferroptosis in NB.
- To elucidate the role of the ESR1/USP7/SREBF1 axis in Gomisin B-induced ferroptosis.
Main Methods:
- Cell viability assays (CCK-8), ferroptosis marker analysis (MDA, GSH, Fe2+, LPO, lipid ROS), co-immunoprecipitation (Co-IP), dual-luciferase reporter assays, ChIP, and in vivo NB mouse models were used.
- SH-SY5Y and IMR-32 cells were treated with RSL3 and Gomisin B to induce ferroptosis.
Main Results:
- Gomisin B promoted ferroptosis in NB cells, an effect reversed by ESR1 overexpression.
- ESR1 transcriptionally activated USP7, which deubiquitinated and stabilized SREBF1, inhibiting ferroptosis.
- Gomisin B regulated the ESR1/USP7/SREBF1 axis to promote NB cell ferroptosis.
- In vivo studies confirmed Gomisin B promoted ferroptosis and inhibited tumor growth in NB-bearing mice.
Conclusions:
- Gomisin B downregulates ESR1, inhibiting USP7 transcriptional activation and SREBF1 deubiquitination.
- This process enhances NB ferroptosis, thereby alleviating NB progression.
- The ESR1/USP7/SREBF1 pathway is a key target for Gomisin B in treating neuroblastoma.
