Identification of pathological-related and diagnostic potential circular RNAs in Stanford type A aortic dissection

IntroductionStanford type A aortic dissection (TAAD) is one of the lethal macrovascular diseases caused by the invasion of blood into the media layer of ascending aortic wall. Inflammation, smooth muscle dysfunction, and extracellular matrix (ECM) degradation were regarded as the major pathology in...

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Main Authors: Qiao Liang, Zeyi Zhou, Hui Li, Qing Tao, Yali Wang, Anqi Lin, Jing Xu, Bin Zhang, Yongzheng Wu, Haiyan Min, Lei Wang, Shiyu Song, Dongjin Wang, Qian Gao
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-01-01
Series:Frontiers in Cardiovascular Medicine
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcvm.2022.1074835/full
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author Qiao Liang
Zeyi Zhou
Hui Li
Qing Tao
Yali Wang
Anqi Lin
Jing Xu
Bin Zhang
Bin Zhang
Yongzheng Wu
Haiyan Min
Lei Wang
Shiyu Song
Dongjin Wang
Qian Gao
author_facet Qiao Liang
Zeyi Zhou
Hui Li
Qing Tao
Yali Wang
Anqi Lin
Jing Xu
Bin Zhang
Bin Zhang
Yongzheng Wu
Haiyan Min
Lei Wang
Shiyu Song
Dongjin Wang
Qian Gao
author_sort Qiao Liang
collection DOAJ
description IntroductionStanford type A aortic dissection (TAAD) is one of the lethal macrovascular diseases caused by the invasion of blood into the media layer of ascending aortic wall. Inflammation, smooth muscle dysfunction, and extracellular matrix (ECM) degradation were regarded as the major pathology in affected tissue. However, the expression pattern and its regulation especially through circular RNAs (circRNAs) as an overall characteristic of TAAD molecular pathology remain unclear.MethodsWe employed CIRCexplorer2 to identify circRNAs based on the RNA sequencing (RNA-seq) data of human ascending aortic tissues to systematically assess the role of circRNA in the massive alterations of gene expression in TAAD aortas. The key circRNAs were determined by LASSO model and functionally annotated by competing endogenous RNAs (ceRNA) network and co-analysis with mRNA profile. The expression level and diagnostic capability of the 4 key circRNAs in peripheral serum were confirmed by real-time polymerase chain reaction (RT-PCR).ResultsThe 4 key circRNAs, namely circPTGR1 (chr9:114341075-114348445[−]), circNOX4 (chr11:89069012-89106660[−]), circAMN1 (chr12:31854796-31862359[−]) and circUSP3 (chr15:63845913-63855207[+]), demonstrated a high power to discriminate between TAAD and control tissues, suggesting that these molecules stand for a major difference between the tissues at gene regulation level. Functionally, the ceRNA network of circRNA-miRNA-mRNA predicted by the online databases, combining gene set enrichment analysis (GSEA) and cell component prediction, revealed that the identified circRNAs covered all the aspects of primary TAAD pathology, centralized with increasing inflammatory factors and cells, and ECM destruction and loss of vascular inherent cells along with the circRNAs. Importantly, we validated the high concentration and diagnostic capability of the 4 key circRNAs in the peripheral serum in TAAD patients.DiscussionThis study reinforces the vital status of circRNAs in TAAD and the possibility of serving as promising diagnostic biomarkers.
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spelling doaj.art-3c8a0d9b28df4a928ebcffa2de6a18b52023-01-13T04:59:31ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2023-01-01910.3389/fcvm.2022.10748351074835Identification of pathological-related and diagnostic potential circular RNAs in Stanford type A aortic dissectionQiao Liang0Zeyi Zhou1Hui Li2Qing Tao3Yali Wang4Anqi Lin5Jing Xu6Bin Zhang7Bin Zhang8Yongzheng Wu9Haiyan Min10Lei Wang11Shiyu Song12Dongjin Wang13Qian Gao14Center for Translational Medicine and Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing, Jiangsu, ChinaDepartment of Thoracic and Cardiovascular Surgery, Institute of Cardiothoracic Vascular Disease, Nanjing University, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, ChinaCenter for Translational Medicine and Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing, Jiangsu, ChinaCenter for Translational Medicine and Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing, Jiangsu, ChinaDepartment of Thoracic and Cardiovascular Surgery, Institute of Cardiothoracic Vascular Disease, Nanjing University, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, ChinaCenter for Translational Medicine and Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing, Jiangsu, ChinaCenter for Translational Medicine and Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing, Jiangsu, ChinaCenter for Translational Medicine and Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing, Jiangsu, ChinaCentral Laboratory, Nanjing Chest Hospital, Nanjing Medical University, Nanjing, ChinaCenter for Translational Medicine and Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing, Jiangsu, ChinaCentral Laboratory, The Second Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Clinical Laboratory, Jiangsu Provincial Hospital of Integrated Chinese and Western Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, ChinaCenter for Translational Medicine and Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing, Jiangsu, ChinaDepartment of Thoracic and Cardiovascular Surgery, Institute of Cardiothoracic Vascular Disease, Nanjing University, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, ChinaCenter for Translational Medicine and Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing, Jiangsu, ChinaIntroductionStanford type A aortic dissection (TAAD) is one of the lethal macrovascular diseases caused by the invasion of blood into the media layer of ascending aortic wall. Inflammation, smooth muscle dysfunction, and extracellular matrix (ECM) degradation were regarded as the major pathology in affected tissue. However, the expression pattern and its regulation especially through circular RNAs (circRNAs) as an overall characteristic of TAAD molecular pathology remain unclear.MethodsWe employed CIRCexplorer2 to identify circRNAs based on the RNA sequencing (RNA-seq) data of human ascending aortic tissues to systematically assess the role of circRNA in the massive alterations of gene expression in TAAD aortas. The key circRNAs were determined by LASSO model and functionally annotated by competing endogenous RNAs (ceRNA) network and co-analysis with mRNA profile. The expression level and diagnostic capability of the 4 key circRNAs in peripheral serum were confirmed by real-time polymerase chain reaction (RT-PCR).ResultsThe 4 key circRNAs, namely circPTGR1 (chr9:114341075-114348445[−]), circNOX4 (chr11:89069012-89106660[−]), circAMN1 (chr12:31854796-31862359[−]) and circUSP3 (chr15:63845913-63855207[+]), demonstrated a high power to discriminate between TAAD and control tissues, suggesting that these molecules stand for a major difference between the tissues at gene regulation level. Functionally, the ceRNA network of circRNA-miRNA-mRNA predicted by the online databases, combining gene set enrichment analysis (GSEA) and cell component prediction, revealed that the identified circRNAs covered all the aspects of primary TAAD pathology, centralized with increasing inflammatory factors and cells, and ECM destruction and loss of vascular inherent cells along with the circRNAs. Importantly, we validated the high concentration and diagnostic capability of the 4 key circRNAs in the peripheral serum in TAAD patients.DiscussionThis study reinforces the vital status of circRNAs in TAAD and the possibility of serving as promising diagnostic biomarkers.https://www.frontiersin.org/articles/10.3389/fcvm.2022.1074835/fullcircular RNAsStanford type A aortic dissectioninflammationextracellular matriximmune infiltration
spellingShingle Qiao Liang
Zeyi Zhou
Hui Li
Qing Tao
Yali Wang
Anqi Lin
Jing Xu
Bin Zhang
Bin Zhang
Yongzheng Wu
Haiyan Min
Lei Wang
Shiyu Song
Dongjin Wang
Qian Gao
Identification of pathological-related and diagnostic potential circular RNAs in Stanford type A aortic dissection
Frontiers in Cardiovascular Medicine
circular RNAs
Stanford type A aortic dissection
inflammation
extracellular matrix
immune infiltration
title Identification of pathological-related and diagnostic potential circular RNAs in Stanford type A aortic dissection
title_full Identification of pathological-related and diagnostic potential circular RNAs in Stanford type A aortic dissection
title_fullStr Identification of pathological-related and diagnostic potential circular RNAs in Stanford type A aortic dissection
title_full_unstemmed Identification of pathological-related and diagnostic potential circular RNAs in Stanford type A aortic dissection
title_short Identification of pathological-related and diagnostic potential circular RNAs in Stanford type A aortic dissection
title_sort identification of pathological related and diagnostic potential circular rnas in stanford type a aortic dissection
topic circular RNAs
Stanford type A aortic dissection
inflammation
extracellular matrix
immune infiltration
url https://www.frontiersin.org/articles/10.3389/fcvm.2022.1074835/full
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