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

CNR Institute of Clinical Physiology, 56124 Pisa, Italy
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2017, 18(11), 2498;
Received: 3 November 2017 / Revised: 20 November 2017 / Accepted: 20 November 2017 / Published: 22 November 2017
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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. View Full-Text
Keywords: miRNome; NGS; BAV; TAV; aortopathy miRNome; NGS; BAV; TAV; aortopathy
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MDPI and ACS Style

Borghini, A.; Foffa, I.; Pulignani, S.; Vecoli, C.; Ait-Ali, L.; Andreassi, M.G. miRNome Profiling in Bicuspid Aortic Valve-Associated Aortopathy by Next-Generation Sequencing. Int. J. Mol. Sci. 2017, 18, 2498.

AMA Style

Borghini A, Foffa I, Pulignani S, Vecoli C, Ait-Ali L, Andreassi MG. miRNome Profiling in Bicuspid Aortic Valve-Associated Aortopathy by Next-Generation Sequencing. International Journal of Molecular Sciences. 2017; 18(11):2498.

Chicago/Turabian Style

Borghini, Andrea, Ilenia Foffa, Silvia Pulignani, Cecilia Vecoli, Lamia Ait-Ali, and Maria G. Andreassi 2017. "miRNome Profiling in Bicuspid Aortic Valve-Associated Aortopathy by Next-Generation Sequencing" International Journal of Molecular Sciences 18, no. 11: 2498.

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