Targeting the Exonic Circular <i>OGT</i> RNA/O-GlcNAc Transferase/Forkhead Box C1 Axis Inhibits Asparagine- and Alanine-Mediated Ferroptosis Repression in Neuroblastoma Progression.

ABSTRACT: The disruption of ferroptosis, an emerging form of programmed cell death, is crucial in the development and aggressiveness of tumors. Meanwhile, the mechanisms and treatments that control ferroptosis in neuroblastoma (NB), a prevalent extracranial cancer in children, are still unknown. In this study, forkhead box C1 (FOXC1) and O-GlcNAc transferase (OGT) are identified as regulators of asparagine- and alanine-mediated ferroptosis repression in NB. Mechanistically, OGT facilitates FOXC1 stabilization via inducing O-GlcNAcylation in liquid condensates to increase the expression of asparagine synthetase (ASNS) and glutamate pyruvate transaminase 2 (GPT2), resulting in asparagine and alanine biogenesis, and subsequent synthesis of cystathionine β-synthase (CBS) or ferritin heavy

SUBMITTER: Li Q 

PROVIDER: S-EPMC12099056 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature