Novel Identified Circular Transcript of RCAN2, circ-RCAN2, Shows Deviated Expression Pattern in Pig Reperfused Infarcted Myocardium and Hypoxic Porcine Cardiac Progenitor Cells In Vitro

Circular RNAs (circRNAs) are crucial in gene regulatory networks and disease development, yet circRNA expression in myocardial infarction (MI) is poorly understood. Here, we harvested myocardium samples from domestic pigs 3 days after closed-chest reperfused MI or sham surgery. Cardiac circRNAs were...

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Main Authors: Julia Mester-Tonczar, Patrick Einzinger, Johannes Winkler, Nina Kastner, Andreas Spannbauer, Katrin Zlabinger, Denise Traxler, Dominika Lukovic, Ena Hasimbegovic, Georg Goliasch, Noemi Pavo, Mariann Gyöngyösi
Format: Article
Language:English
Published: MDPI AG 2021-01-01
Series:International Journal of Molecular Sciences
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Online Access:https://www.mdpi.com/1422-0067/22/3/1390
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author Julia Mester-Tonczar
Patrick Einzinger
Johannes Winkler
Nina Kastner
Andreas Spannbauer
Katrin Zlabinger
Denise Traxler
Dominika Lukovic
Ena Hasimbegovic
Georg Goliasch
Noemi Pavo
Mariann Gyöngyösi
author_facet Julia Mester-Tonczar
Patrick Einzinger
Johannes Winkler
Nina Kastner
Andreas Spannbauer
Katrin Zlabinger
Denise Traxler
Dominika Lukovic
Ena Hasimbegovic
Georg Goliasch
Noemi Pavo
Mariann Gyöngyösi
author_sort Julia Mester-Tonczar
collection DOAJ
description Circular RNAs (circRNAs) are crucial in gene regulatory networks and disease development, yet circRNA expression in myocardial infarction (MI) is poorly understood. Here, we harvested myocardium samples from domestic pigs 3 days after closed-chest reperfused MI or sham surgery. Cardiac circRNAs were identified by RNA-sequencing of rRNA-depleted RNA from infarcted and healthy myocardium tissue samples. Bioinformatics analysis was performed using the CIRIfull and KNIFE algorithms, and circRNAs identified with both algorithms were subjected to differential expression (DE) analysis and validation by qPCR. Circ-RCAN2 and circ-C12orf29 expressions were significantly downregulated in infarcted tissue compared to healthy pig heart. Sanger sequencing was performed to identify the backsplice junctions of circular transcripts. Finally, we compared the expressions of circ-C12orf29 and circ-RCAN2 between porcine cardiac progenitor cells (pCPCs) that were incubated in a hypoxia chamber for different time periods versus normoxic pCPCs. Circ-C12orf29 did not show significant DE in vitro, whereas circ-RCAN2 exhibited significant ischemia-time-dependent upregulation in hypoxic pCPCs. Overall, our results revealed novel cardiac circRNAs with DE patterns in pCPCs, and in infarcted and healthy myocardium. Circ-RCAN2 exhibited differential regulation by myocardial infarction in vivo and by hypoxia in vitro. These results will improve our understanding of circRNA regulation during acute MI.
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spelling doaj.art-d49253552e204667a99fd7387e0a79c92023-12-03T15:21:24ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-01-01223139010.3390/ijms22031390Novel Identified Circular Transcript of RCAN2, circ-RCAN2, Shows Deviated Expression Pattern in Pig Reperfused Infarcted Myocardium and Hypoxic Porcine Cardiac Progenitor Cells In VitroJulia Mester-Tonczar0Patrick Einzinger1Johannes Winkler2Nina Kastner3Andreas Spannbauer4Katrin Zlabinger5Denise Traxler6Dominika Lukovic7Ena Hasimbegovic8Georg Goliasch9Noemi Pavo10Mariann Gyöngyösi11Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, 1090 Vienna, AustriaInstitute of Information Systems Engineering, Research Unit of Information and Software Engineering, Vienna University of Technology, 1040 Vienna, AustriaDepartment of Internal Medicine II, Division of Cardiology, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Internal Medicine II, Division of Cardiology, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Internal Medicine II, Division of Cardiology, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Internal Medicine II, Division of Cardiology, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Internal Medicine II, Division of Cardiology, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Internal Medicine II, Division of Cardiology, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Internal Medicine II, Division of Cardiology, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Internal Medicine II, Division of Cardiology, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Internal Medicine II, Division of Cardiology, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Internal Medicine II, Division of Cardiology, Medical University of Vienna, 1090 Vienna, AustriaCircular RNAs (circRNAs) are crucial in gene regulatory networks and disease development, yet circRNA expression in myocardial infarction (MI) is poorly understood. Here, we harvested myocardium samples from domestic pigs 3 days after closed-chest reperfused MI or sham surgery. Cardiac circRNAs were identified by RNA-sequencing of rRNA-depleted RNA from infarcted and healthy myocardium tissue samples. Bioinformatics analysis was performed using the CIRIfull and KNIFE algorithms, and circRNAs identified with both algorithms were subjected to differential expression (DE) analysis and validation by qPCR. Circ-RCAN2 and circ-C12orf29 expressions were significantly downregulated in infarcted tissue compared to healthy pig heart. Sanger sequencing was performed to identify the backsplice junctions of circular transcripts. Finally, we compared the expressions of circ-C12orf29 and circ-RCAN2 between porcine cardiac progenitor cells (pCPCs) that were incubated in a hypoxia chamber for different time periods versus normoxic pCPCs. Circ-C12orf29 did not show significant DE in vitro, whereas circ-RCAN2 exhibited significant ischemia-time-dependent upregulation in hypoxic pCPCs. Overall, our results revealed novel cardiac circRNAs with DE patterns in pCPCs, and in infarcted and healthy myocardium. Circ-RCAN2 exhibited differential regulation by myocardial infarction in vivo and by hypoxia in vitro. These results will improve our understanding of circRNA regulation during acute MI.https://www.mdpi.com/1422-0067/22/3/1390circRNAcirc-RCAN2AMIporcine model of myocardial infarctionpCPCs
spellingShingle Julia Mester-Tonczar
Patrick Einzinger
Johannes Winkler
Nina Kastner
Andreas Spannbauer
Katrin Zlabinger
Denise Traxler
Dominika Lukovic
Ena Hasimbegovic
Georg Goliasch
Noemi Pavo
Mariann Gyöngyösi
Novel Identified Circular Transcript of RCAN2, circ-RCAN2, Shows Deviated Expression Pattern in Pig Reperfused Infarcted Myocardium and Hypoxic Porcine Cardiac Progenitor Cells In Vitro
International Journal of Molecular Sciences
circRNA
circ-RCAN2
AMI
porcine model of myocardial infarction
pCPCs
title Novel Identified Circular Transcript of RCAN2, circ-RCAN2, Shows Deviated Expression Pattern in Pig Reperfused Infarcted Myocardium and Hypoxic Porcine Cardiac Progenitor Cells In Vitro
title_full Novel Identified Circular Transcript of RCAN2, circ-RCAN2, Shows Deviated Expression Pattern in Pig Reperfused Infarcted Myocardium and Hypoxic Porcine Cardiac Progenitor Cells In Vitro
title_fullStr Novel Identified Circular Transcript of RCAN2, circ-RCAN2, Shows Deviated Expression Pattern in Pig Reperfused Infarcted Myocardium and Hypoxic Porcine Cardiac Progenitor Cells In Vitro
title_full_unstemmed Novel Identified Circular Transcript of RCAN2, circ-RCAN2, Shows Deviated Expression Pattern in Pig Reperfused Infarcted Myocardium and Hypoxic Porcine Cardiac Progenitor Cells In Vitro
title_short Novel Identified Circular Transcript of RCAN2, circ-RCAN2, Shows Deviated Expression Pattern in Pig Reperfused Infarcted Myocardium and Hypoxic Porcine Cardiac Progenitor Cells In Vitro
title_sort novel identified circular transcript of rcan2 circ rcan2 shows deviated expression pattern in pig reperfused infarcted myocardium and hypoxic porcine cardiac progenitor cells in vitro
topic circRNA
circ-RCAN2
AMI
porcine model of myocardial infarction
pCPCs
url https://www.mdpi.com/1422-0067/22/3/1390
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