Silencing of microRNA-106b-5p prevents doxorubicin-mediated cardiotoxicity through modulation of the PR55α/YY1/sST2 signaling axis.
Mol Ther Nucleic Acids
; 32: 704-720, 2023 Jun 13.
Article
em En
| MEDLINE
| ID: mdl-37234747
ABSTRACT
Clinical use of doxorubicin (Dox), an anthracycline with potent anti-tumor effects, is limited because of its highly chemotherapy-induced cardiotoxicity (CIC). After myocardial infarction (MI), we have recently identified Yin Yang-1 (YY1) and histone deacetylase 4 (HDAC4) as two factors involved in the overexpression of the isoform soluble suppression of tumorigenicity 2 (sST2) protein, which acts as a decoy receptor blocking the favorable effects of IL-33. Therefore, high levels of sST2 are associated with increased fibrosis, remodeling, and worse cardiovascular outcomes. No data exist on the role of the YY1/HDAC4/sST2 axis in CIC. This study aimed to evaluate the pathophysiological implication of the molecular YY1/HDAC4/sST2 axis in remodeling that is developed in patients treated with Dox as well as to suggest a novel molecular therapy to prevent anthracycline-induced cardiotoxicity. Here, we have characterized a novel nexus between miR106b-5p (miR-106b) levels and the YY1/HDAC4 axis in relation to the cardiac expression of sST2 using two experimental models with Dox-induced cardiotoxicity. The addition of Dox (5 µM) to human induced pluripotent stem cell-derived cardiomyocytes induced cellular apoptotic death via upregulation of miR-106b-5p (miR-106b), which was confirmed by specific mimic sequences. A functional blockage of miR-106b using the locked nucleic acid antagomir inhibited Dox-induced cardiotoxicity.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Mol Ther Nucleic Acids
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Espanha