CircRNA ARHGAP10 promotes osteogenic differentiation through the miR-335-3p/RUNX2 pathway in aortic valve calcification

Calcific aortic valve disease (CAVD) is a common cardiovascular disease with high morbidity and mortality, and no effective prevention or treatment is available. In recent years, increasing evidence has shown that noncoding RNAs (ncRNAs) play an important role in the pathogenesis and prognosis of CAVD. Several associated circular RNAs (circRNAs) have been reported to be involved in CAVD, such as circRIC3 and TGFBR2. However, the limited number of circRNAs identified in CAVD warrants further in-depth investigation, and the comprehensive elucidation of their role in the key mechanisms of this disease is needed.Through RNA sequencing, we found that circARHGAP10 (hsa_circ_0008975) was highly expressed in calcific aortic valves. CircARHGAP10 knockdown effectively inhibited the extent of osteogenic differentiation of VICs. We then found that circARHGAP10 is a competing endogenous RNA (ceRNA) of miR-355-3p and that miR-355-3p targets RUNX2. In vitro experiments confirmed that circARHGAP10 regulates the osteogenic differentiation of VICs through the miR-355-3p/RUNX2 pathway, and this was validated in vivo using an ApoE-/- mouse model.These findings provide a foundation for circRNA-directed diagnostics and therapeutics for CAVD.