Suppression of circular RNA circDHCR24 alleviates aortic smooth muscle cell proliferation and migration by targeting miR-149-5p/MMP9 axis.

Circular RNAs (circRNAs) are involved in many courses of atherosclerosis and coronary artery disease (CHD). However, the role and effect of circRNAs in vascular restenosis after PCI remains unclear. Human aortic vascular smooth muscle cell (HA-VSMC) was cultured and stimulated with PDGF-BB. The expression profile of circRNAs in HA-VSMCs was screened using microarray analysis. A total 257 aberrantly expressed circRNAs were screened with 2 fold change. Has_circ_0113656 (also called circDHCR24) was validated by qRT-PCR to be significantly up-regulated in PDGF-BB induced HA-VSMCs. CircDHCR24 silencing obviously inhibited the proliferation, migration and phenotypic switch. Moreover, bioinformatics analysis predicted that miR-149-5p had complementary binding sites in 3'-UTR of circDHCR24. Luciferase reporter assay and RIP assay further verified the circDHCR24 acts as a spong for miR-149-5p in HA-VSMCs. Besides, bioinformatics analysis, luciferase reporter assay and RIP assay proved MMP9 was a directly target of miR-149-5p. Finally, cells were transfected with si-circDHCR24 with or without miR-149 inhibitor, and the results showed that co-transfection si-circDHCR24 and miR-149 inhibitor reversed the effect of si-circDHCR24 on cell proliferation, migration and phenotypic switch. Taken together, our study suggested for the first time that the knockdown of circDHCR24 alleviates HA-VSMCs proliferation, migration and phenotypic switching, thereby preventing vascular restenosis.