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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2017
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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. |
format | Online Article Text |
id | pubmed-5713463 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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