Integrated Analysis of the microRNA–mRNA Network Predicts Potential Regulators of Atrial Fibrillation in Humans

Wang, Rong; Bektik, Emre; Sakon, Phraew; Wang, Xiaowei; Huang, Shanying; Meng, Xiangbin; Chen, Mo; Han, Wenqiang; Chen, Jie; Wang, Yanhong; Zhong, Jingquan

doi:10.3390/cells11172629

Cited by 4 publications

(4 citation statements)

References 80 publications

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“…MiRNAs are small noncoding RNAs that negatively regulate target genes and play important roles in the pathophysiology of AF. Wang et al revealed that miR-302b-3p is downregulated in AF and participates in the pathogenesis of AF by suppressing syndecan 1 (SDC-1) transcript levels, suggesting that miR-302b-3p has a potential diagnostic value to distinguish AF patients from healthy individuals ( 29 ). MiR-302c belongs to the miR-302 family, and Bollati et al implicated miR-302c in the development of cardiac hypertrophy, which can lead to atrial structural remodeling ( 30 ).…”

Section: Discussionmentioning

confidence: 99%

Integrated analysis of the lncRNA-miRNA-mRNA network based on competing endogenous RNA in atrial fibrillation

Wang

et al. 2023

Front. Cardiovasc. Med.

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ObjectiveLong non-coding RNAs (lncRNAs) play pivotal roles in the transcriptional regulation of atrial fibrillation (AF) by acting as competing endogenous RNAs (ceRNAs). In the present study, the expression levels of lncRNAs of sinus rhythm (SR) patients and AF patients were investigated with transcriptomics technology, and the lncRNA-miRNA-mRNA network based on the ceRNA theory in AF was elaborated.MethodsLeft atrial appendage (LAA) tissues were obtained from patients with valvular heart disease during cardiac surgery, and they were divided into SR and AF groups. The expression characterizations of differentially expressed (DE) lncRNAs in the two groups were revealed by high-throughput sequencing methods. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed, and the lncRNA-miRNA-mRNA-mediated ceRNA network was constructed.ResultsA total of differentially expressed 82 lncRNAs, 18 miRNAs, and 495 mRNAs in human atrial appendage tissues were targeted. Compared to SR patients, the following changes were found in AF patients: 32 upregulated and 50 downregulated lncRNAs; 7 upregulated and 11 downregulated miRNAs; and 408 upregulated and 87 downregulated mRNAs. A lncRNA-miRNA-mRNA network was constructed, which included 44 lncRNAs, 18 miRNAs, and 347 mRNAs. qRT-PCR was performed to verify these findings. GO and KEGG analyses suggested that inflammatory response, chemokine signaling pathway, and other biological processes play important roles in the pathogenesis of AF. Network analysis based on the ceRNA theory identified that lncRNA XR_001750763.2 and Toll-like receptor 2 (TLR2) compete for binding to miR-302b-3p. In AF patients, lncRNA XR_001750763.2 and TLR2 were upregulated, and miR-302b-3p was downregulated.ConclusionWe identified a lncRNA XR_001750763.2/miR-302b-3p/TLR2 network based on the ceRNA theory in AF. The present study shed light on the physiological functions of lncRNAs and provided information for exploring potential treatments for AF.

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Section: Discussionmentioning

confidence: 99%

Integrated analysis of the lncRNA-miRNA-mRNA network based on competing endogenous RNA in atrial fibrillation

Wang

et al. 2023

Front. Cardiovasc. Med.

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“…and miR-302b-3p are miRNAs that are severely downregulated, with miR-302b-3p being the most extreme. 98…”

Section: Role Of Mir-302/367 Cluster In Drug Sensitivity and Resistancementioning

confidence: 99%

“…The miR‐3b‐1p/SDC‐53 axis may be involved in AF by regulating atrial fibrosis, which is linked to TGF, and p8 is connected to the pro‐fibrotic signaling of EMT98. Both miR‐302b‐3p and miR‐302b‐3p are miRNAs that are severely downregulated, with miR‐302b‐3p being the most extreme 98 …”

Section: Mir‐302/367 Cluster and Other Diseasesmentioning

confidence: 99%

The miR‐302/367 cluster: Aging, inflammation, and cancer

Zhou

Yan²,

Yan

et al. 2023

Cell Biochemistry & Function

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MicroRNAs (miRNAs) are a class of noncoding RNAs that occupy a significant role in biological processes as important regulators of intracellular homeostasis. First, we will discuss the biological genesis and functions of the miR‐302/367 cluster, including miR‐302a, miR‐302b, miR‐302c, miR‐302d, and miR‐367, as well as their roles in physiologically healthy tissues. The second section of this study reviews the progress of the miR‐302/367 cluster in the treatment of cancer, inflammation, and diseases associated with aging. This cluster's aberrant expression in cells and/or tissues exhibits similar or different effects in various diseases through molecular mechanisms such as proliferation, apoptosis, cycling, drug resistance, and invasion. This article also discusses the upstream and downstream regulatory networks of miR‐302/367 clusters and their related mechanisms. Particularly because studies on the upstream regulatory molecules of miR‐302/367 clusters, which include age‐related macular degeneration, myocardial infarction, and cancer, have become more prevalent in recent years. MiR‐302/367 cluster can be an important therapeutic target and the use of miRNAs in combination with other molecular markers may improve diagnostic or therapeutic capabilities, providing unique insights and a more dynamic view of various diseases. It is noted that miRNAs can be an important bio‐diagnostic target and offer a promising method for illness diagnosis, prevention, and treatment.

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“…The functional association for these two miRNAs to AF stems from their reported involvement in sarcomere and calcium remodeling, and fibrosis, respectively [ 47 , 48 ]. Interaction mapping between differentially expressed miRNAs and mRNAs in the RA of PeAF patients suggests suppression of SDC1 expression by miR302b-3p [ 21 ]. This negative interaction was validated in vitro and is reportedly involved in cardiac fibrosis through TGF-β/Smad2 signaling [ 49 , 50 ].…”

Section: Rna Sequencing Studies In Human Af Cohortsmentioning

confidence: 99%

Dissecting the Molecular Mechanisms Driving Electropathology in Atrial Fibrillation: Deployment of RNA Sequencing and Transcriptomic Analyses

Huiskes,

Creemers,

Brundel

2023

Cells

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Despite many efforts to treat atrial fibrillation (AF), the most common progressive and age-related cardiac tachyarrhythmia in the Western world, the efficacy is still suboptimal. A plausible reason for this is that current treatments are not directed at underlying molecular root causes that drive electrical conduction disorders and AF (i.e., electropathology). Insights into AF-induced transcriptomic alterations may aid in a deeper understanding of electropathology. Specifically, RNA sequencing (RNA-seq) facilitates transcriptomic analyses and discovery of differences in gene expression profiles between patient groups. In the last decade, various RNA-seq studies have been conducted in atrial tissue samples of patients with AF versus controls in sinus rhythm. Identified differentially expressed molecular pathways so far include pathways related to mechanotransduction, ECM remodeling, ion channel signaling, and structural tissue organization through developmental and inflammatory signaling pathways. In this review, we provide an overview of the available human AF RNA-seq studies and highlight the molecular pathways identified. Additionally, a comparison is made between human RNA-seq findings with findings from experimental AF model systems and we discuss contrasting findings. Finally, we elaborate on new exciting RNA-seq approaches, including single-nucleotide variants, spatial transcriptomics and profiling of different populations of total RNA, small RNA and long non-coding RNA.

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Integrated Analysis of the microRNA–mRNA Network Predicts Potential Regulators of Atrial Fibrillation in Humans

Cited by 4 publications

References 80 publications

Integrated analysis of the lncRNA-miRNA-mRNA network based on competing endogenous RNA in atrial fibrillation

Integrated analysis of the lncRNA-miRNA-mRNA network based on competing endogenous RNA in atrial fibrillation

The miR‐302/367 cluster: Aging, inflammation, and cancer

Dissecting the Molecular Mechanisms Driving Electropathology in Atrial Fibrillation: Deployment of RNA Sequencing and Transcriptomic Analyses

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