Circ_Mkrn2 facilitates the progression of atrial fibrillation via sponging miR-10b-5p

Chronic intermittent hypoxia (CIH) is the predominant pathophysiological disorder of obstructive sleep apnea (OSA), known to be an important risk factor for atrial fibrillation (AF). MicroRNA-10b-5p levels are significantly reduced under hypoxic conditions. Nevertheless, the role and underlying mechanism of miR-10b-5p in CIH-induced AF remain elusive. In this study, we found that miR-10b-5p expression was downregulated in the atrial tissues of patients and rats with AF. Functionally, miR-10b-5p exerts protective roles in CIH induced atrial fibroblasts activation and AF development by inhibiting the expression of Smad ubiquitin regulatory factor 1 (SMURF1) and TGFβ/Smads signaling activation. RNA sequencing and bioinformatics identified that circ_Mkrn2, as possessing multiple putative binding sites for miR-10b-5p, was increased in patients and rats with AF. Circ_Mkrn2 overexpression promoted SMURF1 expression and atrial fibroblast activation, which were effectively reversed by miR-10b-5p overexpression. Circ_Mkrn2 silencing alleviated the expression of SMURF1 and TGFβ/Smads signaling activation, atrial fibroblasts activation and AF induced by CIH. Our findings showed that circ_Mkrn2 serves as an miR-10b-5p sponge，promotes Smurf1 expression, regulates atrial fibroblast activation, cardiac fibrosis and the development of AF, revealing a potential new target for the prevention of CIH-induced AF.