KIF20A inhibits TRIM21-dependent ubiquitination of DHX9 to boost SOX2 stability, enhancing OSCC stemness and ferroptosis resistance.

ABSTRACT: Oral squamous cell carcinoma (OSCC) is an aggressive malignancy characterized by poor prognosis, largely attributable to cancer stem cell (CSC) persistence and ferroptosis resistance. However, the molecular mechanisms that coordinately regulate stemness maintenance and ferroptosis suppression in OSCC remain insufficiently characterized. In this study, KIF20A was identified as significantly overexpressed in OSCC and strongly correlated with adverse clinical outcomes. An integrative approach identified DHX9 as a candidate interactor of KIF20A. Mechanistic investigations revealed that KIF20A regulates DHX9 nucleocytoplasmic distribution and inhibits TRIM21-mediated K48-linked polyubiquitination at DHX9-K755, thereby preventing its proteasomal degradation and enhancing protein stability. Eleva

SUBMITTER: Zhang Z 

PROVIDER: S-EPMC12920667 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature