Identifying the key microRNAs implicated in atrial fibrillation.

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.