All-trans retinoic acid (ATRA) regulates key genes in the RARG-TOP2B pathway and reduces anthracycline-induced cardiotoxicity.

ABSTRACT: The effectiveness of anthracycline chemotherapeutics (e.g., doxorubicin) is limited by anthracycline-induced cardiotoxicity (ACT). A nonsynonymous variant (S427L) in the retinoic acid receptor-γ (RARG) gene has been associated with ACT. This variant causes reduced RARG activity, which is hypothesized to lead to increased susceptibility to ACT through reduced activation of the retinoic acid pathway. This study explored the effects of activating the retinoic acid pathway using a RAR-agonist, all-trans retinoic acid (ATRA), in human cardiomyocytes and mice treated with doxorubicin. In human cardiomyocytes, ATRA induced the gene expression of RARs (RARG, RARB) and repressed the expression of topoisomerase II enzyme genes (TOP2A, TOP2B), which encode for the molecular targets of anthracyclines

SUBMITTER: Hasbullah JS 

PROVIDER: S-EPMC9635745 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature