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MicroRNA-421 Dysregulation is Associated with Tetralogy of Fallot

The importance of microRNAs for maintaining stability in the developing vertebrate heart has recently become apparent. In addition, there is a growing appreciation for the significance of microRNAs in developmental pathology, including the formation of congenital heart defects. We examined the expre...

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Autores principales: Bittel, Douglas C., Kibiryeva, Nataliya, Marshall, Jennifer A., O’Brien, James E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4197626/
https://www.ncbi.nlm.nih.gov/pubmed/25257024
http://dx.doi.org/10.3390/cells3030713
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author Bittel, Douglas C.
Kibiryeva, Nataliya
Marshall, Jennifer A.
O’Brien, James E.
author_facet Bittel, Douglas C.
Kibiryeva, Nataliya
Marshall, Jennifer A.
O’Brien, James E.
author_sort Bittel, Douglas C.
collection PubMed
description The importance of microRNAs for maintaining stability in the developing vertebrate heart has recently become apparent. In addition, there is a growing appreciation for the significance of microRNAs in developmental pathology, including the formation of congenital heart defects. We examined the expression of microRNAs in right ventricular (RV) myocardium from infants with idiopathic tetralogy of Fallot (TOF, without a 22q11.2 deletion), and found 61 microRNAs to be significantly changed in expression in myocardium from children with TOF compared to normally developing comparison subjects (O’Brien et al. 2012). Predicted targets of microRNAs with altered expression were enriched for gene networks that regulate cardiac development. We previously derived a list of 229 genes known to be critical to heart development, and found 44 had significantly changed expression in TOF myocardium relative to normally developing myocardium. These 44 genes had significant negative correlations with 33 microRNAs, each of which also had significantly changed expression. Here, we focus on miR-421, as it is significantly upregulated in RV tissue from infants with TOF; is predicted to interact with multiple members of cardiovascular regulatory pathways; and has been shown to regulate cell proliferation. We knocked down, and over expressed miR-421 in primary cells derived from the RV of infants with TOF, and infants with normally developing hearts, respectively. We found a significant inverse correlation between the expression of miR-421 and SOX4, a key regulator of the Notch pathway, which has been shown to be important for the cardiac outflow track. These findings suggest that the dysregulation of miR-421 warrants further investigation as a potential contributor to tetralogy of Fallot.
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spelling pubmed-41976262014-10-16 MicroRNA-421 Dysregulation is Associated with Tetralogy of Fallot Bittel, Douglas C. Kibiryeva, Nataliya Marshall, Jennifer A. O’Brien, James E. Cells Brief Report The importance of microRNAs for maintaining stability in the developing vertebrate heart has recently become apparent. In addition, there is a growing appreciation for the significance of microRNAs in developmental pathology, including the formation of congenital heart defects. We examined the expression of microRNAs in right ventricular (RV) myocardium from infants with idiopathic tetralogy of Fallot (TOF, without a 22q11.2 deletion), and found 61 microRNAs to be significantly changed in expression in myocardium from children with TOF compared to normally developing comparison subjects (O’Brien et al. 2012). Predicted targets of microRNAs with altered expression were enriched for gene networks that regulate cardiac development. We previously derived a list of 229 genes known to be critical to heart development, and found 44 had significantly changed expression in TOF myocardium relative to normally developing myocardium. These 44 genes had significant negative correlations with 33 microRNAs, each of which also had significantly changed expression. Here, we focus on miR-421, as it is significantly upregulated in RV tissue from infants with TOF; is predicted to interact with multiple members of cardiovascular regulatory pathways; and has been shown to regulate cell proliferation. We knocked down, and over expressed miR-421 in primary cells derived from the RV of infants with TOF, and infants with normally developing hearts, respectively. We found a significant inverse correlation between the expression of miR-421 and SOX4, a key regulator of the Notch pathway, which has been shown to be important for the cardiac outflow track. These findings suggest that the dysregulation of miR-421 warrants further investigation as a potential contributor to tetralogy of Fallot. MDPI 2014-07-11 /pmc/articles/PMC4197626/ /pubmed/25257024 http://dx.doi.org/10.3390/cells3030713 Text en © 2014 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Brief Report
Bittel, Douglas C.
Kibiryeva, Nataliya
Marshall, Jennifer A.
O’Brien, James E.
MicroRNA-421 Dysregulation is Associated with Tetralogy of Fallot
title MicroRNA-421 Dysregulation is Associated with Tetralogy of Fallot
title_full MicroRNA-421 Dysregulation is Associated with Tetralogy of Fallot
title_fullStr MicroRNA-421 Dysregulation is Associated with Tetralogy of Fallot
title_full_unstemmed MicroRNA-421 Dysregulation is Associated with Tetralogy of Fallot
title_short MicroRNA-421 Dysregulation is Associated with Tetralogy of Fallot
title_sort microrna-421 dysregulation is associated with tetralogy of fallot
topic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4197626/
https://www.ncbi.nlm.nih.gov/pubmed/25257024
http://dx.doi.org/10.3390/cells3030713
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