GINS1 suppresses ferroptosis by inhibiting the Hippo pathway in neuroblastoma.
- 1Department of Pediatric Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China.
- 2Department of Otorhinolaryngology, Wuhan Children's Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Abstract
Background
Neuroblastoma (NBL) prognosis remains poor in high-risk cases. Ferroptosis is a promising therapeutic target, but its regulation in NBL is unclear. This study investigates GINS1's role in NBL ferroptosis.Methods
Bioinformatics analysis (GSE49710, GSE73517, TARGET) assessed GINS1 expression and prognosis. In vitro, GINS1 was knocked down in SH-SY5Y and SK-N-SH cells. Proliferation (CCK-8), migration (Transwell), apoptosis, and ferroptosis markers (lipid peroxidation, Fe²⁺, ACSL4, p-YAP) were evaluated. Rescue experiments involved ACSL4 overexpression.Results
GINS1 knockdown in SH-SY5Y and SK-N-SH cells inhibited proliferation (60% reduction in SH-SY5Y cells and 55% in SK-N-SH cells, p < 0.001), migration (2.1-fold decrease in SH-SY5Y cells and 1.8-fold decrease in SK-N-SH cells, p < 0.001), and induced ferroptosis, evidenced by elevated lipid peroxidation (2.5-fold MDA increase, 1.8-fold Fe²⁺ increase, p < 0.001), upregulation of ACSL4, and increased p-YAP. Mechanistically, GINS1 ablation activates the Hippo pathway (evidenced by increased p-YAP and elevated p-YAP/YAP ratio), leading to YAP inactivation and subsequent derepression of ACSL4, thereby promoting ferroptosis. Rescue experiments confirmed that ACSL4 overexpression in GINS1-overexpressing cells antagonized tumor-promoting effects.Conclusion
GINS1 suppresses ferroptosis via Hippo pathway inhibition and YAP activation, leading to ACSL4 repression. GINS1 is a potential prognostic biomarker and therapeutic target in high-risk NBL.
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BibTeX
@article{gao2026gins1,
title = {{GINS1 suppresses ferroptosis by inhibiting the Hippo pathway in neuroblastoma.}},
author = {Heyun Gao and Yan Wang and Wen Zhang and Geng Li and Yifan Liu and Shanzhen Yu and Yunkai Guo and Tao Hu and Guowei Du},
journal = {Molecular \& cellular oncology},
year = {2026},
month = oct,
doi = {10.1080/23723556.2026.2715868},
url = {https://europepmc.org/article/MED/42903841},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - GINS1 suppresses ferroptosis by inhibiting the Hippo pathway in neuroblastoma.
AU - Heyun Gao
AU - Yan Wang
AU - Wen Zhang
AU - Geng Li
AU - Yifan Liu
AU - Shanzhen Yu
AU - Yunkai Guo
AU - Tao Hu
AU - Guowei Du
PY - 2026
DA - 2026/10/19
JO - Molecular & cellular oncology
DO - 10.1080/23723556.2026.2715868
UR - https://europepmc.org/article/MED/42903841
AB - Background Neuroblastoma (NBL) prognosis remains poor in high-risk cases. Ferroptosis is a promising therapeutic target, but its regulation in NBL is unclear. This study investigates GINS1's role in NBL ferroptosis.Methods Bioinformatics analysis (GSE49710, GSE73517, TARGET) assessed GINS1 expression and prognosis. In vitro, GINS1 was knocked down in SH-SY5Y and SK-N-SH cells. Proliferation (CCK-8), migration (Transwell), apoptosis, and ferroptosis markers (lipid peroxidation, Fe²⁺, ACSL4, p-YAP) were evaluated. Rescue experiments involved ACSL4 overexpression.Results GINS1 knockdown in SH-SY5Y and SK-N-SH cells inhibited proliferation (60% reduction in SH-SY5Y cells and 55% in SK-N-SH cells, p < 0.001), migration (2.1-fold decrease in SH-SY5Y cells and 1.8-fold decrease in SK-N-SH cells, p < 0.001), and induced ferroptosis, evidenced by elevated lipid peroxidation (2.5-fold MDA increase, 1.8-fold Fe²⁺ increase, p < 0.001), upregulation of ACSL4, and increased p-YAP. Mechanistically, GINS1 ablation activates the Hippo pathway (evidenced by increased p-YAP and elevated p-YAP/YAP ratio), leading to YAP inactivation and subsequent derepression of ACSL4, thereby promoting ferroptosis. Rescue experiments confirmed that ACSL4 overexpression in GINS1-overexpressing cells antagonized tumor-promoting effects.Conclusion GINS1 suppresses ferroptosis via Hippo pathway inhibition and YAP activation, leading to ACSL4 repression. GINS1 is a potential prognostic biomarker and therapeutic target in high-risk NBL.
SN - 2372-3556
ER -