Opin vísindi

Novel and annotated long noncoding RNAs associated with ischemia in the human heart

Novel and annotated long noncoding RNAs associated with ischemia in the human heart


Title: Novel and annotated long noncoding RNAs associated with ischemia in the human heart
Author: Ward, Zoe
Schmeier, Sebastian
Saddic, Louis
Sigurðsson, Martin Ingi
Cameron, Vicky A.
Pearson, John
Miller, Allison
Morley‐bunker, Arthur
Gorham, Josh
Seidman, Jonathan G.
... 6 more authors Show all authors
Date: 2021-10-20
Language: English
Scope:
Department: Perioperative Services
Faculty of Medicine
Series: International Journal of Molecular Sciences; 22(21)
ISSN: 1661-6596
DOI: https://doi.org/10.3390/ijms222111324
Subject: Hjartavöðvi; Blóðrás; Kjarnsýrur; Raðgreining; Long noncoding RNA; Myocardial ischemia; RNA sequencing; Catalysis; Molecular Biology; Spectroscopy; Computer Science Applications; Physical and Theoretical Chemistry; Organic Chemistry; Inorganic Chemistry
URI: https://hdl.handle.net/20.500.11815/3040

Show full item record

Citation:

Ward , Z , Schmeier , S , Saddic , L , Sigurðsson , M I , Cameron , V A , Pearson , J , Miller , A , Morley‐bunker , A , Gorham , J , Seidman , J G , Moravec , C S , Sweet , W E , Aranki , S F , Body , S , Muehlschlegel , J D & Pilbrow , A P 2021 , ' Novel and annotated long noncoding RNAs associated with ischemia in the human heart ' , International Journal of Molecular Sciences , vol. 22 , no. 21 , 11324 . https://doi.org/10.3390/ijms222111324

Abstract:

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 p < 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, p = 1 × 10 -23) and activation of cell death pathways ( p < 6 × 10 -9). 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, p = 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.

Description:

Funding Information: This research was supported by the Heart Foundation of New Zealand, the Health Research Council of New Zealand grant number 1746; Canterbury Medical research Foundation grant number 15/04; Lotteries New Zealand Health Research Grant LHR?2018?72291; University of Otago Research Grants; National Heart, Lung, and Blood Institute R01HL150401. Funding Information: Funding: This research was supported by the Heart Foundation of New Zealand, the Health Re‐ search Council of New Zealand grant number 1746; Canterbury Medical research Foundation grant number 15/04; Lotteries New Zealand Health Research Grant LHR‐2018‐72291; University of Otago Research Grants; National Heart, Lung, and Blood Institute R01HL150401. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Files in this item

This item appears in the following Collection(s)