MicroRNA-208a Silencing Attenuates Doxorubicin Induced Myocyte Apoptosis and Cardiac Dysfunction

• Published in: Oxidative medicine and cellular longevity Vol. 2015; no. 2015; pp. 1 - 6
• Main Authors: Tony, Hasahya, Qiutang, Zeng, Yu, Kunwu
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 01.01.2015; Hindawi Limited
• Subjects: Animals; Antibiotics, Antineoplastic - pharmacology; Apoptosis; Apoptosis - drug effects; Cardiomyocytes; Colleges & universities; Down-Regulation - drug effects; Doxorubicin - pharmacology; Echocardiography; Female; GATA4 Transcription Factor - chemistry; GATA4 Transcription Factor - genetics; GATA4 Transcription Factor - metabolism; Gene expression; Heart attacks; Laboratory animals; Medical research; Mice; Mice, Inbred BALB C; MicroRNAs; MicroRNAs - antagonists & inhibitors; MicroRNAs - metabolism; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Oligonucleotides, Antisense - metabolism; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - metabolism; Real-Time Polymerase Chain Reaction; Rodents; Science; Statistical analysis; Stress response; Transcription factors; Up-Regulation - drug effects; China
• ISSN: 1942-0900; 1942-0994
• DOI: 10.1155/2015/597032

Aims. GATA4 depletion is a distinct mechanism by which doxorubicin leads to cardiomyocyte apoptosis, and preservation of GATA4 mitigates doxorubicin induced myocyte apoptosis and cardiac dysfunction. We investigated a novel approach of attenuating doxorubicin induced cardiac toxicity by silencing miR-208a, a heart specific microRNA known to target GATA4. Methods and Results. Eight-week-old female Balb/C mice were randomly assigned to sham, antagomir, and control groups. Antagomir group were pretreated with miR-208a antagomir 4 days before doxorubicin administration. At day 0, control and antagomir groups received 20 mg/kg of doxorubicin, while sham mice received phosphate buffered solution. Echocardiography was done at day 7, after which animals were sacrificed and hearts harvested and assessed for apoptosis and expression of miR-208a, GATA4, and BCL-2. Doxorubicin significantly upregulated miR-208a, downregulated GATA4, and increased myocyte apoptosis, with resulting decrease in cardiac function. In contrast, therapeutic silencing of miR-208a salvaged GATA4 and BCL-2 and decreased apoptosis, with improvement in cardiac function. Conclusion. Doxorubicin upregulates miR-208a and promotes cardiomyocyte apoptosis, while therapeutic silencing of miR-208a attenuates doxorubicin induced myocyte apoptosis with subsequent improvement in cardiac function. These novel results highlight the therapeutic potential of targeting miR-208a to prevent doxorubicin cardiotoxicity.