MiR-21 Protected Cardiomyocytes against Doxorubicin-Induced Apoptosis by Targeting BTG2
Open Access
- 26 June 2015
- journal article
- research article
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 16 (7), 14511-14525
- https://doi.org/10.3390/ijms160714511
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.Keywords
This publication has 32 references indexed in Scilit:
- Breast Cancer Treatment and Adverse Cardiac Events: What Are the Molecular Mechanisms?Cardiology, 2012
- New role of microRNA: carcinogenesis and clinical application in cancerActa Biochimica et Biophysica Sinica, 2011
- MicroRNA-21: From Cancer to Cardiovascular DiseaseCurrent Drug Targets, 2010
- Cardiomyocyte death in doxorubicin-induced cardiotoxicityArchivum Immunologiae et Therapiae Experimentalis, 2009
- MicroRNAs: novel regulators in cardiac development and diseaseCardiovascular Research, 2008
- The functions of animal microRNAsNature, 2004
- Anthracyclines: Molecular Advances and Pharmacologic Developments in Antitumor Activity and CardiotoxicityPublished by American Society for Pharmacology & Experimental Therapeutics (ASPET) ,2004
- Fas-Mediated Apoptosis in Adriamycin-Induced Cardiomyopathy in RatsCirculation, 2000
- Cardiac ultrastructural changes induced by daunorubicin therapyCancer, 1973
- A clinicopathologic analysis of adriamycin cardiotoxicityCancer, 1973