AURKB inhibition induces rhabdomyosarcoma apoptosis and ferroptosis through NPM1/SP1/ACSL5 axis
Related Experiment Video
Updated: May 28, 2025

Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
Published on: March 15, 2024
Huimou Chen1,2,3, Mengzhen Li1,2, Yu Zhang1,2
1Department of Pediatric Oncology and.
Abstract:
Rhabdomyosarcoma (RMS) is one of the most common solid tumors in children and adolescents. Patients with relapsed/refractory RMS have limited treatment options, highlighting the urgency for the identification of novel therapeutic targets for RMS. In the present study, aurora kinase B (AURKB) was found to be highly expressed in RMS and associated with unfavorable prognosis of patients. Functional experiments indicated that inhibition of AURKB significantly reduced RMS cell proliferation, induced apoptosis and ferroptosis, and suppressed RMS growth in vivo. The highly expressed AURKB in RMS contributes to the apoptosis and ferroptosis resistance of tumor cells through the nucleophosmin 1 (NPM1)/Sp1 transcription factor (SP1)/acyl-CoA synthetase long-chain family member 5 (ACSL5) axis. Furthermore, inhibition of AURKB exerted an anti-RMS effect together with vincristine both in vitro and in vivo, with tolerable toxicity. The above findings provide insights we believe are new into the tumorigenesis of RMS, especially with regard to apoptosis or ferroptosis resistance, indicating that AURKB may be a potential target for clinical intervention in patients with RMS.
Insights
Aurora kinase B (AURKB) is highly expressed in pediatric rhabdomyosarcoma (RMS) and drives tumor growth and resistance to cell death. Inhibiting AURKB shows promise as a novel therapeutic strategy for RMS.
Area of Science:
- Pediatric Oncology
- Cancer Biology
- Molecular Therapeutics
Background:
- Rhabdomyosarcoma (RMS) is a common pediatric solid tumor with limited options for relapsed/refractory cases.
- Identifying novel therapeutic targets is crucial for improving RMS treatment outcomes.
Purpose of the Study:
- To investigate the role of aurora kinase B (AURKB) in RMS tumorigenesis.
- To evaluate AURKB as a potential therapeutic target for RMS.
Main Methods:
- Assessed AURKB expression in RMS tissues and correlated it with patient prognosis.
- Performed in vitro and in vivo functional experiments to study the effects of AURKB inhibition on RMS cells.
- Investigated the molecular mechanisms involving the NPM1/SP1/ACSL5 axis.
Main Results:
- AURKB was highly expressed in RMS and linked to poor prognosis.
- AURKB inhibition reduced RMS cell proliferation, induced apoptosis and ferroptosis, and suppressed tumor growth.
- AURKB promotes resistance to apoptosis and ferroptosis via the NPM1/SP1/ACSL5 pathway.
- Combined inhibition of AURKB and vincristine demonstrated synergistic anti-RMS effects with acceptable toxicity.
Conclusions:
- AURKB plays a significant role in RMS development and resistance to cell death.
- AURKB represents a promising therapeutic target for RMS, particularly in combination therapies.
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