A circular RNA derived from the insulin receptor locus protects against doxorubicin-induced cardiotoxicity.

ABSTRACT:

Aims

Cardiotoxicity leading to heart failure (HF) is a growing problem in many cancer survivors. As specific treatment strategies are not available, RNA discovery pipelines were employed and a new and powerful circular RNA (circRNA)-based therapy was developed for the treatment of doxorubicin-induced HF.

Methods and results

The circRNA sequencing was applied and the highly species-conserved circRNA insulin receptor (Circ-INSR) was identified, which participates in HF processes, including those provoked by cardiotoxic anti-cancer treatments. Chemotherapy-provoked cardiotoxicity leads to the down-regulation of Circ-INSR in rodents and patients, which mechanistically contributes to cardiomyocyte cell death, cardiac dysfunction, and mitochondrial damage. In contrast, Circ-INSR o

SUBMITTER: Lu D 

PROVIDER: S-EPMC9637424 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature