Identification of microRNA biomarkers in serum of patients at different stages of atrial fibrillation

Abstract

Background: Atrial fibrillation (AF) is a type of cardiac arrhythmia which is caused by irregular electrical activities in the atria.

Objective: To identify serum microRNA (miRNA) biomarkers at three durations (duration since diagnosis of AF) of AF.

Methods: This study included 14 patients with AF and 8 healthy subjects. The blood sample was collected from each patient at baseline (time of diagnosis) and 12-month and 24-month follow-up periods. The serum was used for miRNA sequencing. The differentially expressed miRNAs (DEMs) between the 3 AF and control groups were independently compared. The predicted target genes of DEMs were subjected to functional enrichment and protein-protein interaction network analyses. Additionally, the miRNA-target gene networks were constructed for the 3 AF groups and miRNA time series analysis was performed. The expression of several key miRNAs was verified by real-time quantitative polymerase chain reaction (qRT-PCR).

Results: In total, 28, 22, and 24 DEMs were identified in the baseline, 12-month, and 24-month groups, respectively. miR-483-5p was the common DEM in the 3 AF groups. In the baseline and 12-month groups, the miR-200b-3p and miR-125b-5p target genes were significantly enriched in the Wnt signaling and several cancer-related pathways, respectively. In the 12-month group, the miR-34a-5p target genes were enriched in the cancer-related pathways. In the miRNA-target gene network, miR-34a-5p regulated the highest number of target genes. The time series analysis revealed that 7 miRNAs, which were downregulated in the control group, were upregulated in the AF groups. The qRT-PCR analysis revealed that the 24-month group exhibited a significant upregulation of miR-483-5p (p < 0.05), whereas the baseline group exhibited significant a downregulation of miR-125b-5p (p < 0.05).

Conclusion: In patients with AF, miR-125b-5p and miR-483-5p can be potential biomarkers of the baseline and 24-month periods, respectively.

Keywords: Atrial fibrillation; KEGG pathway; Target gene; microRNA.