LAUSR

Abstract: Doxorubicin (DOX) is a chemotherapeutic drug for treating various cancers. However, the DOX-induced cardiotoxicity greatly limits its clinical application. MicroRNAs are emerged as critical mediators of cardiomyocyte injury. This work explored the function of miR-215-5p in the regulation of DOX-induced mouse HL-1 cardiomyocyte injury. An in vitro model of DOX-treated cardiotoxicity was established in cardiac mouse cell line HL-1. Gene expression was measured by reverse transcription quantitative polymerase chain reaction. Cell viability was detected using CCK-8. Cell death and apoptosis were tested using transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL), flow cytometry, and caspase-3/7 activity assays. Luciferase reporter assay was used to examine the target of miR-215-5p. We found that DOX induced cardiomyocyte injury and upregulated miR-215-5p in HL-1 cells. Inhibition of miR-215-5p attenuated DOX-induced cardiomyocyte death and apoptosis in vitro. Mechanistical experiments indicated that zinc finger E-box–binding homeobox (ZEB2) was targeted by miR-215-5p. In addition, ZEB2 expression was reduced in DOX-treated HL-1 cells. Rescue assays indicated that ZEB2 knockdown reversed the effects of miR-215-5p inhibition. In conclusion, miR-215-5p inhibition protects HL-1 cells against DOX-induced injury by upregulating ZEB2 expression.