Circ_TGFBR2 Inhibits Vascular Smooth Muscle Cells Phenotypic Switch and Suppresses Aortic Dissection Progression by Sponging miR-29a
Abstract Background: Aortic dissection (AD) is a threatening and catastrophic vascular disease with high mortality rate and limited therapeutic strategies. There is emerging evidence showing that circular RNAs play crucial role in regulating various cardiovascular diseases. However, the biological functions and molecular mechanisms of circRNAs in AD still remains elusive. The purpose of this study was to illustrate the potential functional roles and mechanisms of hsa_circ_0064654(circ_TGFBR2) in vitro and in vivo.Methods:The vascular smooth muscle cells (VSMCs) and AD-VSMCs were isolated from normal aorta and AD tissues. The expression of circ_TGFBR2, miR-29a and KLF4 were detected by Realtime Polymerase Chain Reaction (RT-PCR) and Fluorescence in situ hybridization (FISH). Cell proliferation was assessed by CCK-8 assay, colony formation and EDU assay. Cell migration was evaluated through transwell assay. Dual-luciferase reporter assay and RNA pulldown were performed to identify the interaction among circ_TGFBR2, miR-29a and KLF4. Western Blot measured the expression of phenotype switch-related proteins. AD rat model induced by (β-Aminopropionitrile monofumarate) BAPN was used to verify the role and mechanism of circ_TGFBR2.Results: Circ_TGFBR2 inhibited cell proliferation and migration of AD-VSMCs cells. Overexpression of circ_TGFBR2 promoted the expression of contractile markers(α-SMA,SM22α) and inhibited the expression of synthetic markers (MGP,OPN) in AD-VSMCs cells. Circ_TGFBR2 served as a sponge for miR-29a targeting KLF4. MiR-29a mimics rescue biological roles induced by circ_TGFBR2 overexpression. The results of in vivo experiments were consistent with in vitro experiments.Conclusion:Our study revealed that circ_TGFBR2 regulated VSMCs phenotype switch and suppressed the progression of AD.