MiR-4732-3p was downregulated in breast cancer patients with anthracycline-induced cardiotoxicity, and its administration in doxorubicin-treated rats preserved cardiac function.
Case-Control
Does miR-4732-3p expression correlate with anthracycline-induced cardiotoxicity, and does its therapeutic delivery protect against doxorubicin-induced heart damage?
MiR-4732-3p is a potential novel biomarker for anthracycline-induced cardiotoxicity and a therapeutic target that protects against doxorubicin-induced heart damage in preclinical models.
Anthracycline-induced cardiotoxicity is the most severe collateral effect of chemotherapy originated by an excess of oxidative stress in cardiomyocytes that leads to cardiac dysfunction. We assessed clinical data from patients with breast cancer receiving anthracyclines and searched for discriminating microRNAs between patients that developed cardiotoxicity (cases) and those that did not (controls), using RNA sequencing and regression analysis. Serum levels of 25 microRNAs were differentially expressed in cases versus controls within the first year after anthracycline treatment, as assessed by three different regression models (elastic net, Robinson and Smyth exact negative binomial test and random forest). MiR-4732-3p was the only microRNA identified in all regression models and was downregulated in patients that experienced cardiotoxicity. MiR-4732-3p was also present in neonatal rat cardiomyocytes and cardiac fibroblasts and was modulated by anthracycline treatment. A miR-4732-3p mimic was cardioprotective in cardiac and fibroblast cultures, following doxorubicin challenge, in terms of cell viability and ROS levels. Notably, administration of the miR-4732-3p mimic in doxorubicin-treated rats preserved cardiac function, normalized weight loss, induced angiogenesis, and decreased apoptosis, interstitial fibrosis and cardiac myofibroblasts. At the molecular level, miR-4732-3p regulated genes of TGFβ and Hippo signaling pathways. Overall, the results indicate that miR-4732-3p is a novel biomarker of cardiotoxicity that has therapeutic potential against anthracycline-induced heart damage.
Sánchez-Sánchez et al. (Fri,) conducted a case-control in Anthracycline-induced cardiotoxicity in breast cancer. Anthracycline-induced cardiotoxicity vs. No cardiotoxicity was evaluated on Differential expression of serum microRNAs. MiR-4732-3p was downregulated in breast cancer patients with anthracycline-induced cardiotoxicity, and its administration in doxorubicin-treated rats preserved cardiac function.