Protective Effect of miR-204 on Doxorubicin-Induced Cardiomyocyte Injury via HMGB1.

Youyou Du,Guanghui Liu,Luosha Zhao,Rui Yao,Ding Sheng Jiang

doi:10.1155/2020/8819771

Abstract

The toxicity of doxorubicin (DOX) limits its clinical application. Nevertheless, at present, there is no effective drug to prevent DOX-induced cardiac injury. miR-204 is a newly discovered miRNA with many protective effects on cardiovascular diseases. However, little research has been done on the effects of miR-204 on DOX-induced cardiac injury. Our study is aimed at investigating the effect of miR-204 on DOX-induced myocardial injury. An adenoassociated virus system was used to achieve cardiac-specific overexpression of miR-204. Two weeks later, the mice were intraperitoneally injected with DOX (15 mg/kg) to induce cardiac injury. H9c2 myocardial cells were used to validate the role of miR-204 in vitro. Our study showed that miR-204 expression was decreased in DOX-treated hearts. miR-204 overexpression improved cardiac function and alleviated cardiac inflammation, apoptosis, and autophagy induced by DOX. In addition, our results showed that miR-204 prevented DOX-induced injury in cardiomyocytes by directly decreasing HMGB1 expression. Moreover, the overexpression of HMGB1 could offset the protective effects of miR-204 against DOX-induced cardiac injury. In summary, our study showed that miR-204 protected against DOX-induced cardiac injury via the inhibition of HMGB1, and increasing miR-204 expression may be a new treatment option for patients with DOX-induced cardiac injury.

Highlights

Doxorubicin is currently one of the most effective and widely used anticancer drugs, but its specific cardiotoxicity seriously hinders its clinical application [1]
We further found that miR-204 reduced cell inflammation, apoptosis, and autophagy by directly decreasing high mobility group box 1 (HMGB1) expression
We examined the severity of apoptosis and evaluated the potential signaling pathways related to apoptosis in cardiomyocytes

Summary

Introduction

Doxorubicin is currently one of the most effective and widely used anticancer drugs, but its specific cardiotoxicity seriously hinders its clinical application [1]. Doxorubicin-induced cardiotoxicity involves a variety of mechanisms, including cardiomyocyte apoptosis and autophagy [4, 5]. Many studies have described the potential mechanism of doxorubicin-induced cardiotoxicity, there is still a lack of effective cardioprotective methods available. There is growing evidence that miRNAs are involved in all cardiac functions, including myocardial apoptosis, autophagy, and electrical signal conductance [8]. Clinical and animal studies have shown that miRNAs are potential regulators of DOX-induced cardiotoxicity [9]. MiR-204 has been reported to play a role in regulating apoptosis, inflammation, oncogenesis, and the development of immune cells. The functional and molecular mechanisms of miR-204 in protecting against DOX-induced cardiac injury have not been reported. We investigated the potential functions of miR-204 in DOX-induced cardiac injury. We further found that miR-204 reduced cell inflammation, apoptosis, and autophagy by directly decreasing HMGB1 expression

Materials and Methods

Results

Discussion

Conclusions

Conflicts of Interest