MicroRNA133b alleviates doxorubicininduced cardiomyocyte apoptosis and cardiac fibrosis by targeting PTBP1 and TAGLN2.
Int J Mol Med
; 48(1)2021 Jul.
Article
em En
| MEDLINE
| ID: mdl-33982775
ABSTRACT
Doxorubicin is one of the most important chemotherapeutic drugs for the treatment of malignant tumors, but the cardiotoxicity of doxorubicin severely limits its clinical application. Increasing numbers of microRNAs (miRNAs/miRs) have been found to be dysregulated in doxorubicintreated cardiomyocytes or animal hearts. The current study aimed to investigate the role of miR133b in doxorubicininduced cardiomyocyte injury. Doxorubicin was used to treat HL1 cardiomyocytes to mimic cardiomyocyte injury in vitro. A mouse model of cardiac injury was generated by chronic intraperitoneal injections of doxorubicin. Masson's trichrome staining was performed on cardiac tissues to reveal cardiac fibrosis. Bioinformatics analysis and luciferase reporter assays were applied to explore the downstream targets of miR133b. Flow cytometry and western blotting were conducted to detect cardiomyocyte apoptosis. Protein expression levels of collagen I, III and IV, and fibronectin were detected to reveal extracellular matrix deposition. The results revealed that doxorubicin decreased miR133b expression in the treated HL1 cardiomyocytes and mouse hearts. Overexpression of miR133b restrained cardiomyocyte apoptosis, inhibited collagen accumulation and alleviated cardiac fibrosis in vivo. Mechanistically, polypyrimidine tract binding protein 1 (PTBP1) and transgelin 2 (TAGLN2) were confirmed to bind to miR133b after prediction and screening. Moreover, miR133b negatively regulated the protein expression levels of PTBP1 and TAGLN2. Finally, overexpression of PTBP1 or TAGLN2 reversed the effects of miR133b on apoptosis and collagen accumulation. Thus, the current results indicated that miR133b alleviated doxorubicininduced cardiomyocyte apoptosis and cardiac fibrosis by targeting PTBP1 and TAGLN2, implying that miR133b may be a potential biomarker for doxorubicininduced cardiac injury.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Fibrose
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Regulação da Expressão Gênica
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Apoptose
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Proteína de Ligação a Regiões Ricas em Polipirimidinas
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Ribonucleoproteínas Nucleares Heterogêneas
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MicroRNAs
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Proteínas dos Microfilamentos
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Proteínas Musculares
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article