CircMAPK1 promotes the proliferation and migration of vascular smooth muscle cells through miR-22-3p/ methyl-CpG binding protein 2 axis

Abstract Background and aims Atherosclerosis is a chronic inflammatory disease. The proliferation and migration of vascular smooth muscle cells (VSMCs) contribute to intimal hyperplasia. CircRNAs are class of endogenous RNA and implicated in the various biological processes. However, the role of circRNAs in atherosclerosis remains largely unknown. Methods and results Mice models of atherosclerosis were established using APOE-/- mice fed with high-fat diet. High-throughput sequencing was performed to profile the expression of circRNAs in atherosclerosis. A total of 1289 circRNAs were identified. Six circRNAs were up-regulated and 12 circRNAs were down-regulated in the atherosclerotic plaque tissues. Then we focused on circMAPK1, which showed a high level in atherosclerosis. Silencing circMAPK1 suppressed the proliferation and migration of VSMCs. Further study showed that circMAPK1 bound with miR-22-3p. CircMAPK1 silencing increased the level of miR-22-3p and suppressed the level of MECP2, a known target of miR-22-3p. Interestingly, suppression of miR-22-3p rescued the effect of circMAPK1 silencing on the proliferation and migration of VSMCs. Conclusion CircMPAK1 promoted the proliferation and migration of VSMCs through miR-22-3p/MECP2 axis. Our study revealed the role of circMAPK1 in atherosclerosis and shed lights on the treatment of atherosclerosis.