MiR-21 Protected Cardiomyocytes against Doxorubicin-Induced Apoptosis by Targeting BTG2.
MiR-21 Protected Cardiomyocytes against Doxorubicin-Induced Apoptosis by Targeting BTG2.
复制标题
MiR-21 通过靶向 BTG2 保护心肌细胞免受阿霉素诱导的细胞凋亡。
DOI：
10.3390/ijms160714511
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发表时间：
2015-06-26
影响因子：
5.6
通讯作者：
Xiao X
中科院分区：
文献类型：
--
作者：
Tong Z;Jiang B;Wu Y;Liu Y;Li Y;Gao M;Jiang Y;Lv Q;Xiao X
多柔比星（DOX）是一种具有广谱抗菌活性的蒽环类药物。然而，它会引起心脏细胞毒性，这限制了它的临床应用。microRNA-21（miR-21）在调节细胞增殖和凋亡中起重要作用。虽然miR-21优先在成年心肌细胞中表达并参与心脏发育和心脏疾病，但关于其在响应DOX诱导的心脏细胞毒性中的生物学功能知之甚少。在这项研究中，DOX对小鼠心脏功能和miR-21表达的影响在小鼠心脏组织和大鼠H9 C2心肌细胞中进行了检查。结果显示，与急性DOX损伤小鼠相比，慢性DOX损伤小鼠的心功能更加恶化; DOX处理显著增加了小鼠心脏组织和H9 C2细胞中miR-21的表达。过表达miR-21可减弱阿霉素诱导的心肌细胞凋亡，而敲低其表达可增加阿霉素诱导的心肌细胞凋亡。这些功能获得和丧失实验表明，B细胞易位基因2（BTG 2）是miR-21的靶标。DOX处理后心肌和H9 C2细胞中BTG 2的表达均明显降低。目前的研究表明，miR-21保护小鼠心肌和H9 C2细胞免受DOX诱导的心脏毒性，可能是通过靶向BTG 2。
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.