CircRNA_0263 and circRNA_1507 are dysregulated in a rat model of atrial fibrosis induced by chronic intermittent hypoxia.

ABSTRACT

Aims: This study aimed to characterize circular RNA (circRNA) profiles associated with atrial fibrosis-related atrial fibrillation (AF) and reveal critical circRNAs for AF. Methods: Sprague Dawley rats were randomly divided into control and atrial fibrosis-related AF groups (n = 15 in each group). The rats in the atrial fibrosis-related AF group were induced by chronic intermittent hypoxia (CIH), and then confirmed by electrocardiograms, echocardiography, hematoxylin-eosin staining, Masson staining, immunohistochemistry assays and western blotting. After that, the atrial tissues were sent for circRNA sequencing, and the differentially expressed circRNAs were identified and validated by quantitative real-time polymerase chain reaction (qRT-PCR). Finally, a series of cell experiments were performed to explore the roles of two crucial circRNAs in rat atrial fibroblasts. Results: A CIH-induced AF model was successfully established in the rats. After sequencing, five upregulated and 11 downregulated circRNAs were identified in the CIH-induced AF group. These dysregulated circRNAs were primarily associated with "carbohydrate metabolism" and "cardiovascular diseases". Two circRNAs (circRNA_0263 and circRNA_1507) were predicted to regulate target gene expression by interacting with corresponding miRNAs, including rno-miR-29b-5p, rno-miR-29b-3p, rno-miR-496-5p, rno-miR-136-5p, and novel123-mature. Additionally, circRNA_0263 knockdown and circRNA_1507 overexpression inhibited the cell viability of fibroblasts, and downregulated the expression of fibrosis-related proteins. Conclusion: A series of circRNAs were identified as dysregulated in an AF rat model, and circRNA_0263 and circRNA_1507 might be crucial for atrial fibrosis-related AF development by competing with several miRNAs.