AURKB inhibition induces rhabdomyosarcoma apoptosis and ferroptosis through NPM1/SP1/ACSL5 axis

Huimou Chen1,2,3, Mengzhen Li1,2, Yu Zhang1,2

  • 1Department of Pediatric Oncology and.

JCI Insight
|February 10, 2025
PubMed

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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