Cell Signal. 2026 Jan 29:112400. doi: 10.1016/j.cellsig.2026.112400. Online ahead of print.
ABSTRACT
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.
PMID:41619923 | DOI:10.1016/j.cellsig.2026.112400