Novel and Annotated Long Noncoding RNAs Associated with Ischemia in the Human Heart

Background: Long noncoding RNAs (lncRNAs) have been implicated in the pathogenesis of cardiovascular diseases. We aimed to identify novel lncRNAs associated with the early response to ischemia in the heart. Methods and Results: RNA sequencing data gathered from 81 paired left ventricle samples from...

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Autores principales:	Zoe Ward, Sebastian Schmeier, Louis Saddic, Martin I. Sigurdsson, Vicky A. Cameron, John Pearson, Allison Miller, Arthur Morley-Bunker, Josh Gorham, Jonathan G. Seidman, Christine S. Moravec, Wendy E. Sweet, Sary F. Aranki, Simon Body, Jochen D. Muehlschlegel, Anna P. Pilbrow
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	myocardial ischemia long noncoding RNA RNA sequencing Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/7765e41b132d4aa3a170cc753cab949f
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spelling	oai:doaj.org-article:7765e41b132d4aa3a170cc753cab949f2021-11-11T16:48:34ZNovel and Annotated Long Noncoding RNAs Associated with Ischemia in the Human Heart10.3390/ijms2221113241422-00671661-6596https://doaj.org/article/7765e41b132d4aa3a170cc753cab949f2021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11324https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Background: Long noncoding RNAs (lncRNAs) have been implicated in the pathogenesis of cardiovascular diseases. We aimed to identify novel lncRNAs associated with the early response to ischemia in the heart. Methods and Results: RNA sequencing data gathered from 81 paired left ventricle samples from patients undergoing cardiopulmonary bypass was collected before and after a period of ischemia. Novel lncRNAs were validated with Oxford Nanopore Technologies long-read sequencing. Gene modules associated with an early ischemic response were identified and the subcellular location of selected lncRNAs was determined with RNAscope. A total of 2446 mRNAs, 270 annotated lncRNAs and one novel lncRNA differed in response to ischemia (adjusted <i>p</i> < 0.001, absolute fold change >1.2). The novel lncRNA belonged to a gene module of highly correlated genes that also included 39 annotated lncRNAs. This module associated with ischemia (Pearson correlation coefficient = −0.69, <i>p</i> = 1 × 10<sup>−23</sup>) and activation of cell death pathways (<i>p</i> < 6 × 10<sup>−9</sup>). A further nine novel cardiac lncRNAs were identified, of which, one overlapped five cis-eQTL eSNPs for the gene RWD Domain-Containing Sumoylation Enhancer (RWDD3) and was itself correlated with RWDD3 expression (Pearson correlation coefficient −0.2, <i>p</i> = 0.002). Conclusion: We have identified 10 novel lncRNAs, one of which was associated with myocardial ischemia and may have potential as a novel therapeutic target or early marker for myocardial dysfunction.Zoe WardSebastian SchmeierLouis SaddicMartin I. SigurdssonVicky A. CameronJohn PearsonAllison MillerArthur Morley-BunkerJosh GorhamJonathan G. SeidmanChristine S. MoravecWendy E. SweetSary F. ArankiSimon BodyJochen D. MuehlschlegelAnna P. PilbrowMDPI AGarticlemyocardial ischemialong noncoding RNARNA sequencingBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11324, p 11324 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	myocardial ischemia long noncoding RNA RNA sequencing Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	myocardial ischemia long noncoding RNA RNA sequencing Biology (General) QH301-705.5 Chemistry QD1-999 Zoe Ward Sebastian Schmeier Louis Saddic Martin I. Sigurdsson Vicky A. Cameron John Pearson Allison Miller Arthur Morley-Bunker Josh Gorham Jonathan G. Seidman Christine S. Moravec Wendy E. Sweet Sary F. Aranki Simon Body Jochen D. Muehlschlegel Anna P. Pilbrow Novel and Annotated Long Noncoding RNAs Associated with Ischemia in the Human Heart
description	Background: Long noncoding RNAs (lncRNAs) have been implicated in the pathogenesis of cardiovascular diseases. We aimed to identify novel lncRNAs associated with the early response to ischemia in the heart. Methods and Results: RNA sequencing data gathered from 81 paired left ventricle samples from patients undergoing cardiopulmonary bypass was collected before and after a period of ischemia. Novel lncRNAs were validated with Oxford Nanopore Technologies long-read sequencing. Gene modules associated with an early ischemic response were identified and the subcellular location of selected lncRNAs was determined with RNAscope. A total of 2446 mRNAs, 270 annotated lncRNAs and one novel lncRNA differed in response to ischemia (adjusted <i>p</i> < 0.001, absolute fold change >1.2). The novel lncRNA belonged to a gene module of highly correlated genes that also included 39 annotated lncRNAs. This module associated with ischemia (Pearson correlation coefficient = −0.69, <i>p</i> = 1 × 10<sup>−23</sup>) and activation of cell death pathways (<i>p</i> < 6 × 10<sup>−9</sup>). A further nine novel cardiac lncRNAs were identified, of which, one overlapped five cis-eQTL eSNPs for the gene RWD Domain-Containing Sumoylation Enhancer (RWDD3) and was itself correlated with RWDD3 expression (Pearson correlation coefficient −0.2, <i>p</i> = 0.002). Conclusion: We have identified 10 novel lncRNAs, one of which was associated with myocardial ischemia and may have potential as a novel therapeutic target or early marker for myocardial dysfunction.
format	article
author	Zoe Ward Sebastian Schmeier Louis Saddic Martin I. Sigurdsson Vicky A. Cameron John Pearson Allison Miller Arthur Morley-Bunker Josh Gorham Jonathan G. Seidman Christine S. Moravec Wendy E. Sweet Sary F. Aranki Simon Body Jochen D. Muehlschlegel Anna P. Pilbrow
author_facet	Zoe Ward Sebastian Schmeier Louis Saddic Martin I. Sigurdsson Vicky A. Cameron John Pearson Allison Miller Arthur Morley-Bunker Josh Gorham Jonathan G. Seidman Christine S. Moravec Wendy E. Sweet Sary F. Aranki Simon Body Jochen D. Muehlschlegel Anna P. Pilbrow
author_sort	Zoe Ward
title	Novel and Annotated Long Noncoding RNAs Associated with Ischemia in the Human Heart
title_short	Novel and Annotated Long Noncoding RNAs Associated with Ischemia in the Human Heart
title_full	Novel and Annotated Long Noncoding RNAs Associated with Ischemia in the Human Heart
title_fullStr	Novel and Annotated Long Noncoding RNAs Associated with Ischemia in the Human Heart
title_full_unstemmed	Novel and Annotated Long Noncoding RNAs Associated with Ischemia in the Human Heart
title_sort	novel and annotated long noncoding rnas associated with ischemia in the human heart
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/7765e41b132d4aa3a170cc753cab949f
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Novel and Annotated Long Noncoding RNAs Associated with Ischemia in the Human Heart

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