Integrated Analysis of the microRNA-mRNA Network Predicts Potential Regulators of Atrial Fibrillation in Humans.
Rong WangEmre BektikPhraew SakonXiaowei WangShanying HuangXiangbin MengMo ChenWenqiang HanJie ChenYanhong WangJingquan ZhongPublished in: Cells (2022)
Atrial fibrillation (AF) is a form of sustained cardiac arrhythmia and microRNAs (miRs) play crucial roles in the pathophysiology of AF. To identify novel miR-mRNA pairs, we performed RNA-seq from atrial biopsies of persistent AF patients and non-AF patients with normal sinus rhythm (SR). Differentially expressed miRs (11 down and 9 up) and mRNAs (95 up and 82 down) were identified and hierarchically clustered in a heat map. Subsequently, GO, KEGG, and GSEA analyses were run to identify deregulated pathways. Then, miR targets were predicted in the miRDB database, and a regulatory network of negatively correlated miR-mRNA pairs was constructed using Cytoscape. To select potential candidate genes from GSEA analysis, the top-50 enriched genes in GSEA were overlaid with predicted targets of differentially deregulated miRs. Further, the protein-protein interaction (PPI) network of enriched genes in GSEA was constructed, and subsequently, GO and canonical pathway analyses were run for genes in the PPI network. Our analyses showed that TNF-α, p53, EMT, and SYDECAN1 signaling were among the highly affected pathways in AF samples. SDC-1 (SYNDECAN-1) was the top-enriched gene in p53, EMT, and SYDECAN1 signaling. Consistently, SDC-1 mRNA and protein levels were significantly higher in atrial samples of AF patients. Among negatively correlated miRs, miR-302b-3p was experimentally validated to suppress SDC-1 transcript levels. Overall, our results suggested that the miR-302b-3p/SDC-1 axis may be involved in the pathogenesis of AF.
Keyphrases
- atrial fibrillation
- catheter ablation
- protein protein
- left atrial
- oral anticoagulants
- end stage renal disease
- rna seq
- left atrial appendage
- cell proliferation
- direct oral anticoagulants
- heart failure
- long non coding rna
- ejection fraction
- genome wide
- chronic kidney disease
- newly diagnosed
- small molecule
- peritoneal dialysis
- rheumatoid arthritis
- single cell
- prognostic factors
- long noncoding rna
- epithelial mesenchymal transition
- gene expression
- genome wide identification
- venous thromboembolism
- emergency department
- transcription factor
- left ventricular
- dna methylation
- genome wide analysis
- bioinformatics analysis
- mitral valve
- acute coronary syndrome
- human health
- wastewater treatment
- heat stress