MiR-27a-3p Nanoparticle Alleviate Sunitinib-Induced Cardiotoxicity Through Inhibiting LATS2

Abstract

Damage to cardiac myocytes causes cardiac dysfunction, leading to heart failure or even sudden death with high mortality. As a first-line antitumor drug, Sunitinib has toxic effects on the heart that cannot be ignored. Previous studies have shown that both miR-27a-3p nanoparticle and LATS2 expression can affect cardiac development; however, the role of the cardiotoxicity caused by sunitinib is elusive. Cell viability was detected by MTT, and apoptosis was detected by flow cytometry; mRNA as good as protein expression was tested by qRT-PCR and western blotting; animal models detected cardiac damage; tissue apoptosis was detected by TUNEL staining; the binding site of miR-27a-3p to LATS2 was verified by StarBase as well as dual luciferase reporter gene assay. Our results showed that sunitinib had a toxic effect on cardiomyocytes, which was manifested by reducing cell viability and promoting apoptosis, and this toxic effect was concentration-dependent. In addition, miR-27a-3p expression decreased in sunitinib-treated cardiomyocytes, while mRNA and protein expression of LATS2 increased. Overexpression of miR-27a-3p attenuated sunitinib-induced cardiotoxicity, partially increased cell viability, and inhibited apoptosis. However, miR-27a-3p had binding sites with LATS2, and the mitigating effects of overexpression of miR-27a-3p on cardiotoxicity could all be reversed by overexpression of LATS2. Finally, we verified the cardioprotective effect of overexpression of miR-27a-3p by establishing an animal model. miR-27a-3p alleviates sunitinib-induced cardiotoxicity by inhibiting LATS2, which could be a new strategy for cardiotoxicity treatment in the near future.