Identification and regulation of the long non-coding RNA Heat2 in heart failure

Boeckel, Jes‐Niels; Perret, Maya F.; Glaser, Simone F.; Seeger, Timon; Heumüller, Andreas W.; Chen, Wei; John, David; Kokot, Karoline Elizabeth; Katus, Hugo A.; Haas, Jan; Lackner, Maximilian K.; Kayvanpour, Elham; Grabe, Niels; Dieterich, Christoph; Haehling, Stephan von; Ebner, Nicole; Hünecke, Sabine; Leuschner, Florian; Fichtlscherer, Stephan; Meder, Benjamin; Zeiher, Andreas M.; Dimmeler, Stefanie; Keller, Till

doi:10.1016/j.yjmcc.2018.11.004

Cited by 27 publications

(24 citation statements)

References 38 publications

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“…Furthermore, this study was aimed to explore the relationship between lncRNA expression profiles and cardiac remodeling and dysfunction in HF. According to previous studies, lncRNA expression profiles were significantly dysregulated in ischemic heart disease (Greco et al, 2016), demonstrating their potential as biomarkers of cardiac remodeling (Kumarswamy et al, 2014) and to regulate cellular functions in HF (Boeckel et al, 2019). Our data further suggested that lncRNAs played important roles in the molecular mechanisms of HF and involved in the regulation of diverse cellular processes.…”

Section: Discussionsupporting

confidence: 79%

Comprehensive Analysis and Co-Expression Network of mRNAs and lncRNAs in Pressure Overload-Induced Heart Failure

Chen

Xue

et al. 2019

Front. Genet.

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Aim: Heart failure (HF) is the end stage of various cardiovascular diseases. However, the precise regulation of gene expression profiles and functional mechanisms of long non-coding RNAs (lncRNAs) in HF remain to be elucidated. The present study aimed to identify the differentially expressed profiles and interaction of messenger RNAs (mRNAs) and lncRNAs in pressure overload-induced HF.Methods: Male Sprague-Dawley rats were randomly divided into the HF group and the sham-operated group. HF was induced by the transverse aortic constriction (TAC) surgery. The cardiac expression profiles of mRNAs and lncRNAs in HF were investigated using the microarray. Bioinformatics analyses and co-expression network construction were performed from the RNA sequencing data.Results: The expression profiles of mRNAs and lncRNAs showed significant differences between HF and controls. A total of 147 mRNAs and 162 lncRNAs were identified to be differentially expressed with a fold change of >2 in HF. The relative expression levels of several selected mRNAs and lncRNAs were validated by quantitative PCR. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses indicated that diverse pathways were involved in the molecular mechanisms of cardiac hypertrophy and HF including immune response, smooth muscle contraction, ion transmembrane transport. The mRNA-lncRNA and transcription factors (TFs)-lncRNA co-expression networks were constructed and several genes and TFs were identified as key regulators in the pathogenesis of HF. Further functional prediction showed that the lncRNA NONRATT013999 was predicted to cis-regulate mRNA CDH11, and NONRATT027756 was predicted to trans-regulate HCN4.Conclusion: This study revealed specific expression regulation and potential functions of mRNAs and lncRNAs in pressure overload-induced HF. These results will provide new insights into the underlying mechanisms and potential therapeutic targets for HF.

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Section: Discussionsupporting

confidence: 79%

Comprehensive Analysis and Co-Expression Network of mRNAs and lncRNAs in Pressure Overload-Induced Heart Failure

Chen

Xue

et al. 2019

Front. Genet.

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“…27 Previous studies have shown that lncRNA disorders are associated with a number of heart diseases. [13][14][15][16] Recently, is composed primarily of Kir2.1. Up-regulation of I K1 exerts a great influence on atrial electrophysiology, and I K1 is increased in patients with AF.…”

Section: Discussionmentioning

confidence: 99%

“…It is generally accepted that the noncoding portion rather than the coding portion of the genome may explain the complexity present within higher eukaryotes 27 . Previous studies have shown that lncRNA disorders are associated with a number of heart diseases 13‐16 . Recently, Ruan et al investigated the expression profiles of lncRNAs in AF patients, 28 and Xu Y et al detected the expression levels of lncRNAs during AF in elderly patients 29 .…”

Section: Discussionmentioning

confidence: 99%

“…From a functional perspective, lncRNAs are involved in gene expression and cellular activity through a variety of mechanisms such as chromatin remodelling, titration of transcription factors, sponging of microRNAs (miRNAs), alternative splicing and translational regulation of mRNAs 9‐12 . Dysregulation of lncRNAs has been found to be associated with a number of heart diseases, including myocardial infarction, cardiac hypotrophy and heart failure 13‐16 This suggests a potential use for these lncRNAs as therapeutic targets and/or biomarkers. However, the potential roles and mechanisms of lncRNAs in the context of AF remain poorly studied.…”

Section: Introductionmentioning

confidence: 99%

“…of microRNAs (miRNAs), alternative splicing and translational regulation of mRNAs. [9][10][11][12] Dysregulation of lncRNAs has been found to be associated with a number of heart diseases, including myocardial infarction, cardiac hypotrophy and heart failure [13][14][15][16] This suggests a potential use for these lncRNAs as therapeutic targets and/or biomarkers. However, the potential roles and mechanisms of lncRNAs in the context of AF remain poorly studied.…”

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confidence: 99%

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Long noncoding RNA TCONS‐00106987 promotes atrial electrical remodelling during atrial fibrillation by sponging miR‐26 to regulate KCNJ2

Zhan

Wang

et al. 2020

J Cellular Molecular Medi

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Atrial fibrillation (AF), the most common sustained arrhythmia observed in clinical practice, results in high morbidity and mortality. 1 Current therapies for AF present limitations such as high recurrence, poor tolerance and possible adverse effects. 2 AF is an end result of the atrial remodelling that can occur due to various cardiac disorders. 3 However, AF itself can also induce atrial remodelling, which contributes to the progression of arrhythmia. 4 There are three principal pathophysiological mechanisms that contribute to AF, namely electrical remodelling, structural remodelling and autonomic neural remodelling. 4,5 Electrical remodelling is a significant component of atrial remodelling that occurs early in AF and results in a shortening of both the atrial effective refractory period (AERP) and the action potential duration (APD). 6,7 A large number of studies have shown that left atrial remodelling plays an

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Silenced SOX2‐OT alleviates ventricular arrhythmia associated with heart failure by inhibiting NLRP3 expression via regulating miR‐2355‐3p

Wang

Huang

et al. 2020

Immunity Inflam & Disease

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Background Nucleotide‐binding oligomerization domain‐like receptor family pyrin domain containing 3 (NLRP3) inflammasomes are the most important factors in ventricular arrhythmia associated with heart failure (VA‐HF). However, how the relationship between lncRNA and NLRP3 inflammasomes is regulated in VA‐HF has not been investigated in detail. Thus, we aimed to determine the effects of SOX2‐overlapping transcripts (SOX2‐OT) by targeting NLRP3 in rats with VA‐HF. Methods We established rats (SPF, male, weight: 240 ± 10 g) with VA‐HF by aortic coarctation and constant‐current stimulation, then injected them with small interfering SOX2‐OT and anti‐miR‐2355‐3p. Six weeks later, SOX2‐OT and miR‐2355‐3p expression was measured using the quantitative reverse transcriptase‐polymerase chain reaction and NLRP3, ASC, caspase‐1, IL‐1β, and TGF‐β1 expression were measured by Western blot analysis; the ventricular chambers were histopathologically analyzed by staining with hematoxylin and eosin, Masson trichrome, and Picro Sirius Red and reactive oxygen species (ROS) levels were assessed by flow cytometry. The targeting relationship between miR‐2355‐3p and SOX2‐OT or NLRP3 was verified using dual‐luciferase reporter gene assays. Results The expression of SOX2‐OT and levels of NLRP3 inflammasomes gradually increased in normal rats, and in those with heart failure and with VA‐HF. Silencing SOX2‐OT expression inhibited NLRP3, ASC, caspase‐1, IL‐1β, and TGF‐β1 expression and ROS production, reduced the degrees of cardiomyocyte necrosis and fibrosis and alleviated cardiac dysfunction in rats with VA‐HF. MicroR‐2355‐3p can bind the SOX2‐OT and the 3′‐untranslated region of NLRP3. Inhibiting miR‐2355‐3p reversed the effect of SOX2‐OT in rats with VA‐HF. Conclusions Silencing SOX2‐OT alleviated cardiac dysfunction in rats by reducing the activation of NLRP3 inflammasomes via regulating miR‐2355‐3p.

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Identification and regulation of the long non-coding RNA Heat2 in heart failure

Cited by 27 publications

References 38 publications

Comprehensive Analysis and Co-Expression Network of mRNAs and lncRNAs in Pressure Overload-Induced Heart Failure

Comprehensive Analysis and Co-Expression Network of mRNAs and lncRNAs in Pressure Overload-Induced Heart Failure

Long noncoding RNA TCONS‐00106987 promotes atrial electrical remodelling during atrial fibrillation by sponging miR‐26 to regulate KCNJ2

Silenced SOX2‐OT alleviates ventricular arrhythmia associated with heart failure by inhibiting NLRP3 expression via regulating miR‐2355‐3p

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