Affiliation:
1. Department of General Internal Medicine, Guangxi Medical University Cancer Hospital, Nanning, 530021, Guangxi, PR China
2. Ultrasonic Department, Guangxi Medical University Cancer Hospital, Nanning, 530021, Guangxi, PR China
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.
Publisher
American Scientific Publishers
Subject
Pharmaceutical Science,General Materials Science,Biomedical Engineering,Medicine (miscellaneous),Bioengineering