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Identifying the key microRNAs implicated in atrial fibrillation
1Department of Cardiology, Tianjin Union Medical Center; Tianjin-China.
Objective:
This study investigated the potential microRNAs (miRNAs) having a diagnostic value in atrial fibrillation (AF).
Methods:
The miRNA and mRNA expression profiles of atrial tissue from healthy individuals and patients with AF were downloaded from the Gene Expression Omnibus database. Differentially expressed miRNAs/mRNAs (DEMis/DEMs) were identified in patients with AF. Furthermore, an interaction network between DEMis and DMEs was constructed. The biological processes, molecular functions, and signaling pathways of DEMs were enriched. Then, the diagnostic values of candidate DECs among healthy individuals and patients with AF were preliminarily evaluated in the GSE101586, GSEE101684, and GSE112214 datasets.
Results:
Twenty DEMis were identified in patients with AF, including seven upregulated and 13 downregulated DEMis. Furthermore, 2,307 DEMs were identified in patients with AF. In the DEMi-DEM interaction network, downregulated miR-193b and upregulated miR-16 interacted with the most targeted DEMs, which interacted with 72 and 65 targeted DEMs, respectively. The targeted DEMs were significantly enriched in biological functions including apoptosis and the PI3K-Akt, mTOR, Hippo, HIF-1, and ErbB signaling pathways. Four of the 20 DEMis (i.e., miR-490-3p, miR-630, miR-146b-5p, and miR-367) had a potential value to distinguish patients with AF from healthy individuals in the GSE68475, GSE70887, and GSE28954 datasets. The area under the curve values for those four DEMis were 0.751, 0.719, 0.709, and 0.7, respectively.
Conclusion:
DEMis might play key roles in AF progression through the mTOR and Hippo signaling pathways. miR-409-3p, miR-630, miR-146b-5p, and miR-367 had a potential diagnostic value to discriminate patients with AF from healthy controls in this study.
Insights
This study identified specific microRNAs (miRNAs) that show potential for diagnosing atrial fibrillation (AF). Four miRNAs, including miR-490-3p, were found to effectively distinguish AF patients from healthy individuals.
Area of Science:
- Biochemistry
- Genetics
- Molecular Biology
Background:
- Atrial fibrillation (AF) is a common arrhythmia with complex underlying mechanisms.
- MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and are implicated in various cardiovascular diseases, including AF.
- Identifying reliable biomarkers for AF diagnosis is crucial for timely intervention and management.
Purpose of the Study:
- To investigate the potential diagnostic value of specific microRNAs (miRNAs) in atrial fibrillation (AF).
- To identify differentially expressed miRNAs (DEMis) and their target genes in AF.
- To explore the role of these miRNAs and their associated pathways in AF pathogenesis.
Main Methods:
- Analysis of miRNA and mRNA expression profiles from atrial tissue of AF patients and healthy controls using Gene Expression Omnibus (GEO) data.
- Identification of differentially expressed miRNAs (DEMis) and mRNAs (DEMs).
- Construction of a DEMi-DEM interaction network and enrichment analysis of targeted DEMs' biological functions and signaling pathways.
- Evaluation of the diagnostic performance of candidate miRNAs in independent datasets.
Main Results:
- Twenty differentially expressed miRNAs (DEMis) were identified in AF patients (7 upregulated, 13 downregulated).
- Downregulated miR-193b and upregulated miR-16 showed extensive interactions within the regulatory network.
- Targeted DEMs were significantly enriched in pathways such as apoptosis, PI3K-Akt, mTOR, Hippo, HIF-1, and ErbB signaling.
- Four miRNAs (miR-490-3p, miR-630, miR-146b-5p, and miR-367) demonstrated potential in distinguishing AF patients from healthy individuals, with AUC values ranging from 0.7 to 0.751.
Conclusions:
- Differentially expressed miRNAs (DEMis) may play significant roles in the progression of atrial fibrillation (AF), particularly through the mTOR and Hippo signaling pathways.
- The identified miRNAs, specifically miR-409-3p, miR-630, miR-146b-5p, and miR-367, show promise as potential diagnostic biomarkers for discriminating AF patients from healthy controls.
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