Affiliation:
1. Department of Vascular Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
2. Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
Abstract
Imatinib is a classical targeted drug to treat chronic myeloid leukemia (CML). However, it shows cardiotoxicity, which limits its clinical application. Long noncoding RNA (lncRNA) maternally expressed gene 3 (MEG3) shows proapoptotic properties in human cells. This study is performed to investigate whether targeting MEG3 can attenuate imatinib-mediated cardiotoxicity to cardiomyocytes. In this work, H9c2 cells were divided into four groups: control group, hypoxia group, hypoxia + imatinib, and hypoxia + imatinib + MEG3 knockdown group. MEG3 and microRNA-129-5p (miR-129-5p) expression levels were detected by the quantitative real-time PCR (qRT-PCR). The viability and apoptosis of H9c2 cells were then evaluated by cell counting kit-8 (CCK-8), flow cytometry, and TUNEL assays. The targeting relationships between MEG3 and miR-129-5p, between miR-129-5p and high-mobility group box 1 (HMBG1), were validated by dual-luciferase reporter assay and RNA Immunoprecipitation (RIP) assay. The protein expression level of HMGB1 was detected by western blot. It was revealed that, Imatinib-inhibited cell viability and aggravated the apoptosis of H9c2 cells cultured in hypoxic condition, and MEG3 knockdown significantly counteracted this effect. MiR-129-5p was a downstream target of MEG3 and it directly targeted HMGB1, and knockdown of MEG3 inhibited HMGB1 expression in H9c2 cells. In conclusion, targeting MEG3 ameliorates imatinib-induced injury of cardiomyocytes via regulating miR-129-5p/HMGB1 axis.
Subject
Cancer Research,Cell Biology,Molecular Medicine,General Medicine,Pathology and Forensic Medicine