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miRNome Profiling in Bicuspid Aortic Valve-Associated Aortopathy by Next-Generation Sequencing

The molecular mechanisms underlying thoracic aortic aneurysm (TAA) in patients with bicuspid aortic valve (BAV) are incompletely characterized. MicroRNAs (miRNAs) may play a major role in the different pathogenesis of aortopathy. We sought to employ next-generation sequencing to analyze the entire m...

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Autores principales: Borghini, Andrea, Foffa, Ilenia, Pulignani, Silvia, Vecoli, Cecilia, Ait-Ali, Lamia, Andreassi, Maria Grazia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5713463/
https://www.ncbi.nlm.nih.gov/pubmed/29165337
http://dx.doi.org/10.3390/ijms18112498
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author Borghini, Andrea
Foffa, Ilenia
Pulignani, Silvia
Vecoli, Cecilia
Ait-Ali, Lamia
Andreassi, Maria Grazia
author_facet Borghini, Andrea
Foffa, Ilenia
Pulignani, Silvia
Vecoli, Cecilia
Ait-Ali, Lamia
Andreassi, Maria Grazia
author_sort Borghini, Andrea
collection PubMed
description The molecular mechanisms underlying thoracic aortic aneurysm (TAA) in patients with bicuspid aortic valve (BAV) are incompletely characterized. MicroRNAs (miRNAs) may play a major role in the different pathogenesis of aortopathy. We sought to employ next-generation sequencing to analyze the entire miRNome in TAA tissue from patients with BAV and tricuspid aortic valve (TAV). In the discovery stage, small RNA sequencing was performed using the Illumina MiSeq platform in 13 TAA tissue samples (seven patients with BAV and six with TAV). Gene ontology (GO) and KEGG pathway analysis were used to identify key pathways and biological functions. Validation analysis was performed by qRT-PCR in an independent cohort of 30 patients with BAV (26 males; 59.5 ± 12 years) and 30 patients with TAV (16 males; 68.5 ± 9.5 years). Bioinformatic analysis identified a total of 489 known mature miRNAs and five novel miRNAs. Compared to TAV samples, 12 known miRNAs were found to be differentially expressed in BAV, including two up-regulated and 10 down-regulated (FDR-adjusted p-value ≤ 0.05 and fold change ≥  1.5). GO and KEGG pathway enrichment analysis (FDR-adjusted p-value < 0.05) identified different target genes and pathways linked to BAV and aneurysm formation, including Hippo signaling pathway, ErbB signaling, TGF-beta signaling and focal adhesion. Validation analysis of selected miRNAs confirmed the significant down-regulation of miR-424-3p (p = 0.01) and miR-3688-3p (p = 0.03) in BAV patients as compared to TAV patients. Our study provided the first in-depth screening of the whole miRNome in TAA specimens and identified specific dysregulated miRNAs in BAV patients.
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spelling pubmed-57134632017-12-07 miRNome Profiling in Bicuspid Aortic Valve-Associated Aortopathy by Next-Generation Sequencing Borghini, Andrea Foffa, Ilenia Pulignani, Silvia Vecoli, Cecilia Ait-Ali, Lamia Andreassi, Maria Grazia Int J Mol Sci Article The molecular mechanisms underlying thoracic aortic aneurysm (TAA) in patients with bicuspid aortic valve (BAV) are incompletely characterized. MicroRNAs (miRNAs) may play a major role in the different pathogenesis of aortopathy. We sought to employ next-generation sequencing to analyze the entire miRNome in TAA tissue from patients with BAV and tricuspid aortic valve (TAV). In the discovery stage, small RNA sequencing was performed using the Illumina MiSeq platform in 13 TAA tissue samples (seven patients with BAV and six with TAV). Gene ontology (GO) and KEGG pathway analysis were used to identify key pathways and biological functions. Validation analysis was performed by qRT-PCR in an independent cohort of 30 patients with BAV (26 males; 59.5 ± 12 years) and 30 patients with TAV (16 males; 68.5 ± 9.5 years). Bioinformatic analysis identified a total of 489 known mature miRNAs and five novel miRNAs. Compared to TAV samples, 12 known miRNAs were found to be differentially expressed in BAV, including two up-regulated and 10 down-regulated (FDR-adjusted p-value ≤ 0.05 and fold change ≥  1.5). GO and KEGG pathway enrichment analysis (FDR-adjusted p-value < 0.05) identified different target genes and pathways linked to BAV and aneurysm formation, including Hippo signaling pathway, ErbB signaling, TGF-beta signaling and focal adhesion. Validation analysis of selected miRNAs confirmed the significant down-regulation of miR-424-3p (p = 0.01) and miR-3688-3p (p = 0.03) in BAV patients as compared to TAV patients. Our study provided the first in-depth screening of the whole miRNome in TAA specimens and identified specific dysregulated miRNAs in BAV patients. MDPI 2017-11-22 /pmc/articles/PMC5713463/ /pubmed/29165337 http://dx.doi.org/10.3390/ijms18112498 Text en © 2017 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 (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Borghini, Andrea
Foffa, Ilenia
Pulignani, Silvia
Vecoli, Cecilia
Ait-Ali, Lamia
Andreassi, Maria Grazia
miRNome Profiling in Bicuspid Aortic Valve-Associated Aortopathy by Next-Generation Sequencing
title miRNome Profiling in Bicuspid Aortic Valve-Associated Aortopathy by Next-Generation Sequencing
title_full miRNome Profiling in Bicuspid Aortic Valve-Associated Aortopathy by Next-Generation Sequencing
title_fullStr miRNome Profiling in Bicuspid Aortic Valve-Associated Aortopathy by Next-Generation Sequencing
title_full_unstemmed miRNome Profiling in Bicuspid Aortic Valve-Associated Aortopathy by Next-Generation Sequencing
title_short miRNome Profiling in Bicuspid Aortic Valve-Associated Aortopathy by Next-Generation Sequencing
title_sort mirnome profiling in bicuspid aortic valve-associated aortopathy by next-generation sequencing
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5713463/
https://www.ncbi.nlm.nih.gov/pubmed/29165337
http://dx.doi.org/10.3390/ijms18112498
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