Tabriz University of Medical Sciences Journal of Cardiovascular and Thoracic Research 2008-5117 17 2 2025 06 28 An integrated bioinformatics approach for identification of key modulators and biomarkers involved in atrial fibrillation 109 120 10.34172/jcvtr.025.33347 EN Summan Thahiem https://orcid.org/0009-0001-1637-503X Ayesha Ishtiaq https://orcid.org/0000-0003-1244-3223 Faisal Iftekhar https://orcid.org/0009-0003-5587-0919 Muhammad Ishtiaq Jan https://orcid.org/0000-0003-2770-3040 Iram Murtaza https://orcid.org/0000-0001-8092-5211 Journal Article 10.34172/jcvtr.025.33347 2024 09 19 2025 04 19 Introduction: Atrial fibrillation (AFib) is a sustained form of cardiac arrythmia that occurs due to sympathetic overdrive, neurohumoral and electrophysiological changes. Sympatho-renal modulatory approach via miRNA-based therapeutics is likely to be an important treatment option for AFib. The study was aimed to unravel the common miRNAs as therapeutic targets involved in sympatho- renovascular axis to combat AFib. Methods: We employed the bioinformatics approach to discover differentially expressed genes (DEGs) from microarray gene expression datasets GSE41177 and GSE79768 of AFib patients. Concomitantly, genes associated with sympathetic cardio-renal axis, from Genetic Testing Registry (GTR) of National Center for Biotechnology Information (NCBI) were also analyzed. Overlapping miRNAs that target the maximum number of genes across all three pathological conditions perpetuating AFib were shortlisted. To confirm the reliability of the identified miRNAs, differential expression analysis was performed on miRNA expression profiles GSE190898, GSE68475, GSE70887 and GSE28954 derived from AFib patient samples. Results: ShinyGO analysis revealed enrichment in beta-adrenergic signaling, calcium signaling, as well as G protein-coupled receptor (GPCR) signaling involved in post synaptic membrane potential. The intersection of top 10 modules in miRNA-mRNA network revealed hub miRNAs having highest node degree, maximum neighborhood component (MNC), and maximal clique centrality (MCC) scores. Differential expression analysis revealed hub miRNAs identified through integrated approach were found to be significantly dysregulated in AFib patients. Conclusion: This integrated approach identified 6 hub miRNAs, 4 reported (miR-101-3p, miR-23-3p, miR-27-3p, miR-25-3p) and 2 novel (miR-32-5p, miR-92-3p) miRNAs that might act as putative biomarkers for AFib.