CircUBE4B attenuates AngII-induced vascular smooth muscle cell proliferation and migration through upregulating GSK3B by sponging miR-199a-5p.

Aortic dissection (AD) is a life-threatening medical condition generally affecting those 65-75 years of age with poor outcome and various complications. It is urgent to investigate the pathogenesis of AD to explore novel diagnostic markers and therapeutic targets for AD. Pathological vascular remodeling due to dysregulated proliferation and migration of vascular smooth muscle cells (VSMCs) would promote AD development. Glycogen synthase kinase 3 beta (GSK3B) could suppress VSMC proliferation and migration. However, the effect of GSK3B on VSMCs and the mechanism regulating GSK3B in AD remains unclear. Here, circRNA and miRNA profiles in aortic tissues were identified by RNA sequencing, human VSMCs were treated with angiotensin II (AngII) to established AD model in vitro, and the regulatory network among circular RNA (circRNA), microRNA (miRNA) and mRNA was determined by dual-luciferase reporter gene assay. Our results revealed that circUBE4B was downregulated in aortic tissues of AD patients and AngII-treated VSMCs. Besides, circUBE4B and GSK3B were decreased yet miR-199a-5p was increased in AngII-treated VSMCs. Moreover, circUBE4B increased GSK3B level by targeting miR-199a-5p in VSMCs. In addition, circUBE4B attenuated AngII-induced VSMC proliferation and migration through GSK3B by sponging miR-199a-5p. In summary, these findings might provide novel diagnostic markers and therapeutic targets for AD.