MiR-27b-3p ameliorates DOX-induced cardiotoxicity by suppressing myocardial inflammation and oxidative stress in mice and cardiomyocytes

Doxorubicin (DOX), a chemotherapeutic drug used for Cancer treatment, faces limitations in clinical use due to its cardiotoxicity. The study intended to investigate the effect of MicroRNA (miR)-27b-3p on DOX-induced cardiotoxicity. Quantitative polymerase chain reaction was conducted to identify the miR-27b-3p expression in cardiac tissues of 24 mice exposure to doxorubicin for 0-7days. To investigate the functions of miR-27b-3p, the remaining 40 mice were assigned into 4 experimental groups (n=10 per group): Control+miR-scramble, Control+miR-27b-3p, chronic heart failure (CHF) + miR-scramble, and CHF+miR-27b-3p. Specifically, C57BL/6J mice received a tail vein injection of adeno-associated viral 9 (AAV9)-miR-27b-3p/miR-scramble and/or intraperitoneal injection of 15mg/kg DOX. Echocardiography was used to measure basic cardiac function parameters. Hematoxylin-eosin and Sirius red staining were performed to assess cardiac structural changes and fibrotic areas. For cellular experiments, neonatal mouse cardiomyocytes were exposure to 5μg/ml DOX. The levels of inflammatory factors and oxidative stress indicators in cardiac tissues or cardiomyocytes were assessed by western blotting, enzyme-linked immunosorbent assay, or corresponding detection kits. The results showed that miR-27b-3p expression was downregulated in mouse cardiac tissues following DOX treatment. Overexpression of miR-27b-3p improved cardiac function and ameliorated pathological changes in mice. In addition, DOX-induced myocardial inflammation and oxidative stress were mitigated by miR-27b-3p overexpression both in vivo and in vitro. MiR-27b-3p negatively regulated the expression of four target genes (PLK2, Adora2b, Apaf1 and Nrk) in DOX-stimulated cardiomyocytes. In conclusion, miR-27b-3p ameliorates DOX-induced cardiac dysfunction and myocardial injury by inhibiting inflammation and oxidative stress.

DOX; cardiotoxicity; fibrosis; inflammation; miR-27b-3p; oxidative stress.