Possible key microRNAs and corresponding molecular mechanisms for atrial fibrillation

Zhang, Huili; Yang, Guang-Hong; Zhong, Nanshan; Shan, Jun; Li, Xiaona; Wu, Yanhai; Xu, Yang; Yuan, Ye

doi:10.14744/anatoljcardiol.2020.39483

Cited by 4 publications

(4 citation statements)

References 43 publications

(48 reference statements)

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“…Oxidative stress is one of the important mechanisms required for the initiation and maintenance of AF. Zhang et al ( 21 ) reported that miR-223-3p regulates the activation of paired box 6, resulting in apoptosis, a mechanism that plays a significant role in the progression of the prothrombotic state in AF. Novel evidence has suggested that the inhibition of miR-223-3p expression could upregulate the expression of FOXO3 and activate the autophagy pathway, thereby significantly inhibiting myocardial fibrosis and improving myocardial remodeling in AF ( 22 ).…”

Section: Resultsmentioning

confidence: 99%

lncRNA KCNQ1OT1 may function as a competitive endogenous RNA in atrial fibrillation by sponging miR‑223‑3p

et al. 2021

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Atrial fibrillation (AF) is one of the most common forms of cardiac arrhythmia. Novel evidence has indicated that a competing endogenous RNA (ceRNA) mechanism may occur in AF. The present study aimed to identify differentially expressed microRNAs (miRNAs/miRs) in AF and predict their targeting long non-coding RNAs (lncRNAs) to identify a potential ceRNA network involved in AF using bioinformatics analysis. The GSE68475 microarray dataset was downloaded from the Gene Expression Omnibus database and differentially expressed miRNAs in AF were obtained. In addition, right atrial appendage (RAA) tissues from patients with AF were collected to determine the expression levels of the miRNAs identified following bioinformatics analysis using reverse transcription-quantitative PCR (n=8 per group). Subsequently, Gene Ontology (GO) functional term and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analyses of the target genes of differentially expressed miRNAs of interest were performed. The potential upstream lncRNAs targeting the identified miRNAs were predicted using bioinformatics analysis. A dual luciferase reporter assay was used to verify the existence of a targeted relationship between the differentially expressed miRNA and lncRNA of interest. The results identified 43 differentially expressed miRNAs, including 23 upregulated miRNAs. The trends in the expression levels of miR-223-3p were inconsistent between the microarray data and those recorded in the RAA tissues from patients with persistent AF. Therefore, miR-223-3p was selected as the miRNA of interest for further investigations. The target gene of miR-233-3p was found to be enriched in 57 GO terms and 21 KEGG signaling pathways. According to the bioinformatics prediction, 69 lncRNAs targeting miR-223-3p were identified, including the lncRNA growth arrest-specific transcript 5, lncRNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) and lncRNA MYC-induced long non-coding RNA. The results from dual luciferase assay confirmed that miR-223-3p was a direct target of KCNQ1OT1. A ceRNA regulatory relationship may exist between KCNQ1OT1 and miR-223-3p in AF, providing therefore a novel potential research target for further studies.

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Section: Resultsmentioning

confidence: 99%

lncRNA KCNQ1OT1 may function as a competitive endogenous RNA in atrial fibrillation by sponging miR‑223‑3p

et al. 2021

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“… 28 , 29 However, few researchers have focused on the function of the Hippo signaling pathway in AF. Zhang et al 30 and Li and coworkers 31 suggested the role of the Hippo signaling pathway in AF regulation by bioinformatics analysis. Dysregulation of the Hippo signaling pathway in the cardiovascular system has been reported to be associated with myocardial infarction (MI), cardiac hypertrophy and vascular remodeling.…”

Section: Discussionmentioning

confidence: 99%

Identification of Differentially Expressed Genes and Pathways in Human Atrial Fibrillation by Bioinformatics Analysis

Pan¹,

Zhou²,

Xiao³

et al. 2022

IJGM

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Introduction: Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia, but the molecular mechanisms underlying AF are not known. We aimed to identify the pivotal genes and pathways involved in AF pathogenesis because they could become potential biomarkers and therapeutic targets of AF. Methods: The microarray datasets of GSE31821 and GSE41177 were downloaded from the Gene Expression Omnibus database. After combining the two datasets, differentially expressed genes (DEGs) were screened by the Limma package. MicroRNAs (miRNAs) confirmed experimentally to have an interaction with AF were screened through the miRTarBase database. Target genes of miRNAs were predicted using the miRNet database, and the intersection between DEGs and target genes of miRNAs, which were defined as common genes (CGs), were analyzed. Functional and pathway-enrichment analyses of DEGs and CGs were performed using the databases DAVID and KOBAS. Protein-protein interaction (PPI) network, miRNA-messenger(m) RNA network, and drug-gene network was visualized. Finally, reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) was used to validate the expression of hub genes in the miRNA-mRNA network. Results: Thirty-three CGs were acquired from the intersection of 65 DEGs from the integrated dataset and 9777 target genes of miRNAs. Fifteen "hub" genes were selected from the PPI network, and the miRNA-mRNA network, including 82 miRNAs and 9 target mRNAs, was constructed. Furthermore, with the validation by RT-qPCR, macrophage migration inhibitory factor (MIF), MYC proto-oncogene, bHLH transcription factor (MYC), inhibitor of differentiation 1 (ID1), and C-X-C Motif Chemokine Receptor 4 (CXCR4) were upregulated and superoxide Dismutase 2 (SOD2) was downregulated in patients with AF compared with healthy controls. We also found MIF, MYC, and ID1 were enriched in the transforming growth factor (TGF)-β and Hippo signaling pathway. Conclusion:We identified several pivotal genes and pathways involved in AF pathogenesis. MIF, MYC, and ID1 might participate in AF progression through the TGF-β and Hippo signaling pathways. Our study provided new insights into the mechanisms of action of AF.

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“…PAX6 and AHRARNT have emerged as interesting nodes in the regulatory network constructed by searching for interaction between transcription factors and miRNAs targets associated with the development of atrial fibrillation 76 . More specifically, when comparing AF patients with controls, PAX6 was found to be regulated by the downregulation of miR-223-3p, probably through the modulation of AHRARNT transcription factor activity.…”

Section: Variations In Transcription Factor Activity Profilesmentioning

confidence: 99%

A meta-analysis approach to gene regulatory network inference identifies key regulators of cardiovascular diseases

Pepe,

Appierdo,

Ausiello

et al. 2024

Preprint

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Cardiovascular diseases (CVDs) represent a major concern for global health whose mechanistic understanding is complicated by a complex interplay between genetic predisposition and environmental factors.Specifically, heart failure (HF), encompassing dilated cardiomyopathy (DC), ischemic cardiomyopathy (ICM), and hypertrophic cardiomyopathy (HCM), is a topic of substantial interest in basic and clinical research. Here we used a Partial Correlation Coefficient-based algorithm (PCC) within the context of a meta-analysis framework, to construct a Gene Regulatory Network (GRN) that identifies key regulators whose activity is perturbed in Heart Failure. By integrating data from multiple independent studies, our approach unveiled crucial regulatory associations between transcription factors (TFs) and structural genes, emphasizing their pivotal roles in regulating metabolic pathways, such as fatty acid metabolism, oxidative stress response, epithelial-to-mesenchymal transition, and coagulation. In addition to known associations, our analysis also identified novel regulators, including the identification of TFs FPM315 and MOVO-B, which are implicated in dilated cardiomyopathies, and TEAD1 and TEAD2 in both dilated and ischemic cardiomyopathies. Moreover, we uncovered alterations in adipogenesis and oxidative phosphorylation pathways in hypertrophic cardiomyopathy, and discovered a role for IL2 STAT5 signaling in heart failure.Our findings underscore the importance of TFs activity in the initiation and progression of cardiac disease, highlighting their potential as pharmacological targets.

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Possible key microRNAs and corresponding molecular mechanisms for atrial fibrillation

Cited by 4 publications

References 43 publications

lncRNA KCNQ1OT1 may function as a competitive endogenous RNA in atrial fibrillation by sponging miR‑223‑3p

lncRNA KCNQ1OT1 may function as a competitive endogenous RNA in atrial fibrillation by sponging miR‑223‑3p

Identification of Differentially Expressed Genes and Pathways in Human Atrial Fibrillation by Bioinformatics Analysis

A meta-analysis approach to gene regulatory network inference identifies key regulators of cardiovascular diseases

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