Dysregulation of microRNA Modulatory Network in Abdominal Aortic Aneurysm

Abdominal artery aneurysm (AAA) refers to abdominal aortic dilatation of 3 cm or greater. AAA is frequently underdiagnosed due to often asymptomatic character of the disease, leading to elevated mortality due to aneurysm rupture. MiRNA constitute a pool of small RNAs controlling gene expression and...

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Main Authors: Daniel P. Zalewski, Karol P. Ruszel, Andrzej Stępniewski, Dariusz Gałkowski, Jacek Bogucki, Łukasz Komsta, Przemysław Kołodziej, Paulina Chmiel, Tomasz Zubilewicz, Marcin Feldo, Janusz Kocki, Anna Bogucka-Kocka
Format: Article
Language:English
Published: MDPI AG 2020-06-01
Series:Journal of Clinical Medicine
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Online Access:https://www.mdpi.com/2077-0383/9/6/1974
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author Daniel P. Zalewski
Karol P. Ruszel
Andrzej Stępniewski
Dariusz Gałkowski
Jacek Bogucki
Łukasz Komsta
Przemysław Kołodziej
Paulina Chmiel
Tomasz Zubilewicz
Marcin Feldo
Janusz Kocki
Anna Bogucka-Kocka
author_facet Daniel P. Zalewski
Karol P. Ruszel
Andrzej Stępniewski
Dariusz Gałkowski
Jacek Bogucki
Łukasz Komsta
Przemysław Kołodziej
Paulina Chmiel
Tomasz Zubilewicz
Marcin Feldo
Janusz Kocki
Anna Bogucka-Kocka
author_sort Daniel P. Zalewski
collection DOAJ
description Abdominal artery aneurysm (AAA) refers to abdominal aortic dilatation of 3 cm or greater. AAA is frequently underdiagnosed due to often asymptomatic character of the disease, leading to elevated mortality due to aneurysm rupture. MiRNA constitute a pool of small RNAs controlling gene expression and is involved in many pathologic conditions in human. Targeted panel detecting altered expression of miRNA and genes involved in AAA would improve early diagnosis of this disease. In the presented study, we selected and analyzed miRNA and gene expression signatures in AAA patients. Next, generation sequencing was applied to obtain miRNA and gene-wide expression profiles from peripheral blood mononuclear cells in individuals with AAA and healthy controls. Differential expression analysis was performed using DESeq2 and uninformative variable elimination by partial least squares (UVE-PLS) methods. A total of 31 miRNAs and 51 genes were selected as the most promising biomarkers of AAA. Receiver operating characteristics (ROC) analysis showed good diagnostic ability of proposed biomarkers. Genes regulated by selected miRNAs were determined in silico and associated with functional terms closely related to cardiovascular and neurological diseases. Proposed biomarkers may be used for new diagnostic and therapeutic approaches in management of AAA. The findings will also contribute to the pool of knowledge about miRNA-dependent regulatory mechanisms involved in pathology of that disease.
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spelling doaj.art-b79d409c6c8d402b89495a17836cfc8f2023-11-20T04:48:48ZengMDPI AGJournal of Clinical Medicine2077-03832020-06-0196197410.3390/jcm9061974Dysregulation of microRNA Modulatory Network in Abdominal Aortic AneurysmDaniel P. Zalewski0Karol P. Ruszel1Andrzej Stępniewski2Dariusz Gałkowski3Jacek Bogucki4Łukasz Komsta5Przemysław Kołodziej6Paulina Chmiel7Tomasz Zubilewicz8Marcin Feldo9Janusz Kocki10Anna Bogucka-Kocka11Chair and Department of Biology and Genetics, Medical University of Lublin, 4a Chodźki St., 20-093 Lublin, PolandChair of Medical Genetics, Department of Clinical Genetics, Medical University of Lublin, 11 Radziwiłłowska St., 20-080 Lublin, PolandEcotech Complex Analytical and Programme Centre for Advanced Environmentally Friendly Technologies, University of Marie Curie-Skłodowska, 39 Głęboka St., 20-612 Lublin, PolandDepartment of Pathology and Laboratory Medicine, Rutgers - Robert Wood Johnson Medical School, One Robert Wood Johnson Place, New Brunswick, NJ 08903-0019, USAChair of Medical Genetics, Department of Clinical Genetics, Medical University of Lublin, 11 Radziwiłłowska St., 20-080 Lublin, PolandChair and Department of Medicinal Chemistry, Medical University of Lublin, 4 Jaczewskiego St., 20-090 Lublin, PolandLaboratory of Diagnostic Parasitology, Chair and Department of Biology and Genetics, Medical University of Lublin, 4a Chodźki St., 20-093 Lublin, PolandChair and Department of Biology and Genetics, Medical University of Lublin, 4a Chodźki St., 20-093 Lublin, PolandChair and Department of Vascular Surgery and Angiology, Medical University of Lublin, 11 Staszica St., 20-081 Lublin, PolandChair and Department of Vascular Surgery and Angiology, Medical University of Lublin, 11 Staszica St., 20-081 Lublin, PolandChair of Medical Genetics, Department of Clinical Genetics, Medical University of Lublin, 11 Radziwiłłowska St., 20-080 Lublin, PolandChair and Department of Biology and Genetics, Medical University of Lublin, 4a Chodźki St., 20-093 Lublin, PolandAbdominal artery aneurysm (AAA) refers to abdominal aortic dilatation of 3 cm or greater. AAA is frequently underdiagnosed due to often asymptomatic character of the disease, leading to elevated mortality due to aneurysm rupture. MiRNA constitute a pool of small RNAs controlling gene expression and is involved in many pathologic conditions in human. Targeted panel detecting altered expression of miRNA and genes involved in AAA would improve early diagnosis of this disease. In the presented study, we selected and analyzed miRNA and gene expression signatures in AAA patients. Next, generation sequencing was applied to obtain miRNA and gene-wide expression profiles from peripheral blood mononuclear cells in individuals with AAA and healthy controls. Differential expression analysis was performed using DESeq2 and uninformative variable elimination by partial least squares (UVE-PLS) methods. A total of 31 miRNAs and 51 genes were selected as the most promising biomarkers of AAA. Receiver operating characteristics (ROC) analysis showed good diagnostic ability of proposed biomarkers. Genes regulated by selected miRNAs were determined in silico and associated with functional terms closely related to cardiovascular and neurological diseases. Proposed biomarkers may be used for new diagnostic and therapeutic approaches in management of AAA. The findings will also contribute to the pool of knowledge about miRNA-dependent regulatory mechanisms involved in pathology of that disease.https://www.mdpi.com/2077-0383/9/6/1974abdominal aortic aneurysmAAAmiRNAmicroRNAgeneexpression
spellingShingle Daniel P. Zalewski
Karol P. Ruszel
Andrzej Stępniewski
Dariusz Gałkowski
Jacek Bogucki
Łukasz Komsta
Przemysław Kołodziej
Paulina Chmiel
Tomasz Zubilewicz
Marcin Feldo
Janusz Kocki
Anna Bogucka-Kocka
Dysregulation of microRNA Modulatory Network in Abdominal Aortic Aneurysm
Journal of Clinical Medicine
abdominal aortic aneurysm
AAA
miRNA
microRNA
gene
expression
title Dysregulation of microRNA Modulatory Network in Abdominal Aortic Aneurysm
title_full Dysregulation of microRNA Modulatory Network in Abdominal Aortic Aneurysm
title_fullStr Dysregulation of microRNA Modulatory Network in Abdominal Aortic Aneurysm
title_full_unstemmed Dysregulation of microRNA Modulatory Network in Abdominal Aortic Aneurysm
title_short Dysregulation of microRNA Modulatory Network in Abdominal Aortic Aneurysm
title_sort dysregulation of microrna modulatory network in abdominal aortic aneurysm
topic abdominal aortic aneurysm
AAA
miRNA
microRNA
gene
expression
url https://www.mdpi.com/2077-0383/9/6/1974
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