Circ_RUSC2 upregulates the expression of miR-661 target gene SYK and regulates the function of vascular smooth muscle cells

Abstract

Many studies have identified circRNA as a prospective direction in the field of cardiovascular research. Detection of circRNA expression in different vascular smooth muscle cell (VSMC) phenotypes revealed that circ_RUSC2 is upregulated in proliferative VSMCs. Sequence analysis of circ_RUSC2 showed that there are multiple binding sites of miR-661 on circ_RUSC2, and that SYK is an important target gene of miR-661. MiR-661 expression is downregulated in proliferative VSMCs, whereas the expression of SYK is upregulated. Circ_RUSC2 and miR-661 do not affect each other’s expression levels, but circ_RUSC2 can promote the expression of SYK and inhibit the expression of SM22-alpha, whereas miR-661 has the opposite effect. At the same time, VSMC proliferation and migration can be promoted by SYK or circ_RUSC2, but the linear sequence of circ_RUSC2 can not. MiR-661 and circ_RUSC2 siRNAs inhibit VSMC proliferation and migration, and promote cell apoptosis. When an miR-661 mimic or SYK siRNAs were co-transfected with circ_RUSC2 overexpression vector, VSMC proliferation, apoptosis, and migration were not significantly altered. Accordingly, circ_RUSC2 can promote the expression of SYK, a target gene of miR-661, and regulate VSMC proliferation, apoptosis, phenotypic modulation, and migration. These findings will supply a theoretical basis for studying circRNA function in VSMCs, and new ideas for the diagnosis and treatment of cardiovascular diseases.