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Cripto Is Targeted by miR-1a-3p in a Mouse Model of Heart Development

During cardiac differentiation, numerous factors contribute to the development of the heart. Understanding the molecular mechanisms underlying cardiac development will help combat cardiovascular disorders, among the leading causes of morbidity and mortality worldwide. Among the main mechanisms, we i...

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Autores principales: Angrisano, Tiziana, Varrone, Francesca, Ragozzino, Elvira, Fico, Annalisa, Minchiotti, Gabriella, Brancaccio, Mariarita
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10419258/
https://www.ncbi.nlm.nih.gov/pubmed/37569627
http://dx.doi.org/10.3390/ijms241512251
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author Angrisano, Tiziana
Varrone, Francesca
Ragozzino, Elvira
Fico, Annalisa
Minchiotti, Gabriella
Brancaccio, Mariarita
author_facet Angrisano, Tiziana
Varrone, Francesca
Ragozzino, Elvira
Fico, Annalisa
Minchiotti, Gabriella
Brancaccio, Mariarita
author_sort Angrisano, Tiziana
collection PubMed
description During cardiac differentiation, numerous factors contribute to the development of the heart. Understanding the molecular mechanisms underlying cardiac development will help combat cardiovascular disorders, among the leading causes of morbidity and mortality worldwide. Among the main mechanisms, we indeed find Cripto. Cripto is found in both the syncytiotrophoblast of ampullary pregnancies and the inner cell mass along the primitive streak as the second epithelial–mesenchymal transformation event occurs to form the mesoderm and the developing myocardium. At the same time, it is now known that cardiac signaling pathways are intimately intertwined with the expression of myomiRNAs, including miR-1. This miR-1 is one of the muscle-specific miRs; aberrant expression of miR-1 plays an essential role in cardiac diseases. Given this scenario, our study aimed to evaluate the inverse correlation between Cripto and miR-1 during heart development. We used in vitro models of the heart, represented by embryoid bodies (EBs) and embryonic carcinoma cell lines derived from an embryo-derived teratocarcinoma in mice (P19 cells), respectively. First, through a luciferase assay, we demonstrated that Cripto is a target of miR-1. Following this result, we observed that as the days of differentiation increased, the Cripto gene expression decreased, while the level of miR-1 increased; furthermore, after silencing miR-1 in P19 cells, there was an increase in Cripto expression. Moreover, inducing damage with a cobra cardiotoxin (CTX) in post-differentiation cells, we noted a decreased miR-1 expression and increased Cripto. Finally, in mouse cardiac biopsies, we observed by monitoring gene expression the distribution of Cripto and miR-1 in the right and left ventricles. These results allowed us to detect an inverse correlation between miR-1 and Cripto that could represent a new pharmacological target for identifying new therapies.
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spelling pubmed-104192582023-08-12 Cripto Is Targeted by miR-1a-3p in a Mouse Model of Heart Development Angrisano, Tiziana Varrone, Francesca Ragozzino, Elvira Fico, Annalisa Minchiotti, Gabriella Brancaccio, Mariarita Int J Mol Sci Article During cardiac differentiation, numerous factors contribute to the development of the heart. Understanding the molecular mechanisms underlying cardiac development will help combat cardiovascular disorders, among the leading causes of morbidity and mortality worldwide. Among the main mechanisms, we indeed find Cripto. Cripto is found in both the syncytiotrophoblast of ampullary pregnancies and the inner cell mass along the primitive streak as the second epithelial–mesenchymal transformation event occurs to form the mesoderm and the developing myocardium. At the same time, it is now known that cardiac signaling pathways are intimately intertwined with the expression of myomiRNAs, including miR-1. This miR-1 is one of the muscle-specific miRs; aberrant expression of miR-1 plays an essential role in cardiac diseases. Given this scenario, our study aimed to evaluate the inverse correlation between Cripto and miR-1 during heart development. We used in vitro models of the heart, represented by embryoid bodies (EBs) and embryonic carcinoma cell lines derived from an embryo-derived teratocarcinoma in mice (P19 cells), respectively. First, through a luciferase assay, we demonstrated that Cripto is a target of miR-1. Following this result, we observed that as the days of differentiation increased, the Cripto gene expression decreased, while the level of miR-1 increased; furthermore, after silencing miR-1 in P19 cells, there was an increase in Cripto expression. Moreover, inducing damage with a cobra cardiotoxin (CTX) in post-differentiation cells, we noted a decreased miR-1 expression and increased Cripto. Finally, in mouse cardiac biopsies, we observed by monitoring gene expression the distribution of Cripto and miR-1 in the right and left ventricles. These results allowed us to detect an inverse correlation between miR-1 and Cripto that could represent a new pharmacological target for identifying new therapies. MDPI 2023-07-31 /pmc/articles/PMC10419258/ /pubmed/37569627 http://dx.doi.org/10.3390/ijms241512251 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Angrisano, Tiziana
Varrone, Francesca
Ragozzino, Elvira
Fico, Annalisa
Minchiotti, Gabriella
Brancaccio, Mariarita
Cripto Is Targeted by miR-1a-3p in a Mouse Model of Heart Development
title Cripto Is Targeted by miR-1a-3p in a Mouse Model of Heart Development
title_full Cripto Is Targeted by miR-1a-3p in a Mouse Model of Heart Development
title_fullStr Cripto Is Targeted by miR-1a-3p in a Mouse Model of Heart Development
title_full_unstemmed Cripto Is Targeted by miR-1a-3p in a Mouse Model of Heart Development
title_short Cripto Is Targeted by miR-1a-3p in a Mouse Model of Heart Development
title_sort cripto is targeted by mir-1a-3p in a mouse model of heart development
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10419258/
https://www.ncbi.nlm.nih.gov/pubmed/37569627
http://dx.doi.org/10.3390/ijms241512251
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