title: MiR-21 Protected Cardiomyocytes against Doxorubicin-Induced Apoptosis by Targeting BTG2.
abstract: Doxorubicin (DOX) is an anthracycline drug with a wide spectrum of antineoplastic activities. However, it causes cardiac cytotoxicity, and this limits its clinical applications. MicroRNA-21 (miR-21) plays a vital role in regulating cell proliferation and apoptosis. While miR-21 is preferentially expressed in adult cardiomyocytes and involved in cardiac development and heart disease, little is known regarding its biological functions in responding to DOX-induced cardiac cytotoxicity. In this study, the effects of DOX on mouse cardiac function and the expression of miR-21 were examined in both mouse heart tissues and rat H9C2 cardiomyocytes. The results showed that the cardiac functions were more aggravated in chronic DOX injury mice compared with acute DOX-injury mice; DOX treatment significantly increased miR-21 expression in both mouse heart tissue and H9C2 cells. Over-expression of miR-21 attenuated DOX-induced apoptosis in cardiamyocytes whereas knocking down its expression increased DOX-induced apoptosis. These gain- and loss- of function experiments showed that B cell translocation gene 2 (BTG2) was a target of miR-21. The expression of BTG2 was significantly decreased both in myocardium and H9C2 cells treated with DOX. The present study has revealed that miR-21 protects mouse myocardium and H9C2 cells against DOX-induced cardiotoxicity probably by targeting BTG2.
authors.affiliation: Department of Pathology, the Second Xiangya Hospital, Central South University, Changsha 410000, Hunan, China. tongzhongyi2008@163.com.|Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha 410000, Hunan, China. tongzhongyi2008@163.com.
authors.forename: Zhongyi
authors.initials: Z
authors.lastname: Tong
authors.affiliation: Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha 410000, Hunan, China. jiangbimei@163.com.
authors.forename: Bimei
authors.initials: B
authors.lastname: Jiang
authors.affiliation: Food Science and Technology College, Hunan Agricultural University, Changsha 410000, Hunan, China. wuyanyang2002@126.com.
authors.forename: Yanyang
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha 410000, Hunan, China. LYB820812@126.com.
authors.forename: Yanjuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha 410000, Hunan, China. LYB820812@126.com.
authors.forename: Yuanbin
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha 410000, Hunan, China. gaomin201404@126.com.
authors.forename: Min
authors.initials: M
authors.lastname: Gao
authors.affiliation: Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha 410000, Hunan, China. jiangyu146@126.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha 410000, Hunan, China. lvqinglan2014@163.com.
authors.forename: Qinglan
authors.initials: Q
authors.lastname: Lv
authors.affiliation: Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha 410000, Hunan, China. xiaoxianzhong@csu.edu.cn.
authors.forename: Xianzhong
authors.initials: X
authors.lastname: Xiao
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D017209:Apoptosis; D002460:Cell Line; D002478:Cells, Cultured; D004317:Doxorubicin / Q000009:adverse effects*; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; C521959:BTG2 protein, rat; D017874:Immediate-Early Proteins; D035683:MicroRNAs; D025521:Tumor Suppressor Proteins; C546082:mirn21 microRNA, rat; D004317:Doxorubicin
keywords: B cell translocation gene 2 (BTG-2); cardiotoxicity; doxorubicin (DOX); microRNA-21 (miR-21)