Circ_0001946 facilitates the proliferation and represses apoptosis of ox-LDL-stimulated Vascular Smooth Muscle Cells via regulating miR-641/CCND1 pathway.

Recently, circRNAs are reported to exhibit significant regulation on atherosclerosis development. Circ_0001946 has been identified in several diseases and our present study was aimed to investigate its biological roles on Vascular Smooth Muscle Cells (VSMCs) incubated with ox-LDL. In our research, we validated circ_0001946 was obviously increased in human atherosclerosis patient serums. ox-LDL induced circ_0001946 expression in VSMCs. Meanwhile, we reported miR-641 was obviously decreased in atherosclerosis serum samples compared to the health controls. It was indicated silence of circ_0001946 repressed VSMCs proliferation and contributed to the cell apoptosis. In addition, we observed that down-regulation of circ_0001946 induced miR-641 expression greatly and their direct correlation was proved using dual-luciferase reporter assay. Inhibitors of miR-641 rescued the effects of depletion of circ_0001946 on proliferation and apoptosis in VSMCs treated by ox-LDL. In addition, amplification and overexpression of cyclin D1 (CCND1), which can alter cell cycle progression, is dys-regulated in a variety of diseases. It was showed that CCND1 could be a target of miR-641 and circ_0001946 acted as a sponge of miR-641 to increase CCND1 level. In conclusion, our current data suggested circ_0001946 silence inhibited VSMCs proliferation and increased cell apoptosis through modulating miR-641 and CCND1.