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Silencing of microRNA-106b-5p prevents doxorubicin-mediated cardiotoxicity through modulation of the PR55α/YY1/sST2 signaling axis.
Lax, Antonio; Soler, Fernando; Fernandez Del Palacio, Maria Josefa; Pascual-Oliver, Silvia; Ballester, Miriam Ruiz; Fuster, Jose Javier; Pascual-Figal, Domingo; Asensio-Lopez, Maria Del Carmen.
Afiliación
  • Lax A; Biomedical Research Institute Virgen de la Arrixaca (IMIB-Arrixaca), University of Murcia, 30120 Murcia, Spain.
  • Soler F; Biomedical Research Institute Virgen de la Arrixaca (IMIB-Arrixaca), University of Murcia, 30120 Murcia, Spain.
  • Fernandez Del Palacio MJ; Veterinary Hospital, University of Murcia 30100 Murcia, Spain.
  • Pascual-Oliver S; Biomedical Research Institute Virgen de la Arrixaca (IMIB-Arrixaca), University of Murcia, 30120 Murcia, Spain.
  • Ballester MR; Biomedical Research Institute Virgen de la Arrixaca (IMIB-Arrixaca), University of Murcia, 30120 Murcia, Spain.
  • Fuster JJ; Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, Spain.
  • Pascual-Figal D; Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, Spain.
  • Asensio-Lopez MDC; Cardiology Department, Hospital Virgen de la Arrixaca, IMIB-Arrixaca and University of Murcia, 30120 Murcia, Spain.
Mol Ther Nucleic Acids ; 32: 704-720, 2023 Jun 13.
Article en En | MEDLINE | ID: mdl-37234747
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Mol Ther Nucleic Acids Año: 2023 Tipo del documento: Article País de afiliación: España Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Mol Ther Nucleic Acids Año: 2023 Tipo del documento: Article País de afiliación: España Pais de publicación: Estados Unidos