Preservation of ALYREF Phase Separation Mitigates Doxorubicin-Induced Cardiomyocyte DNA Damage and Cardiotoxicity.

ABSTRACT: The clinical utility of the anticancer agent doxorubicin (DOX) is limited by its dose-dependent cardiotoxicity. ALYREF, a nuclear protein that preserves genomic stability through interactions with intranuclear components or as an m⁵C-binding regulator of mRNA maturation and export, has not been previously implicated in DOX-induced cardiotoxicity (DIC). Here, the role and underlying mechanisms of ALYREF in the pathogenesis of DIC are investigated. The findings demonstrate that ALYREF expression is markedly reduced in a murine model of DIC. Myocardial-specific overexpression of ALYREF attenuates DOX-induced DNA damage and cardiomyocyte apoptosis, whereas cardiac-specific knockout of ALYREF (ALYREF CKO) exacerbates DOX-induced cardiac dysfunction. Mechanistically, it is identified that nuclea

SUBMITTER: Gao X 

PROVIDER: S-EPMC12631900 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature