Role of miR-181b/Notch1 Axis in circ_TNPO1 Promotion of Proliferation and Migration of Atherosclerotic Vascular Smooth Muscle Cells.

Background: The role and expression level change in circ_TNPO1 (hsa_circ_0072951) in atherosclerosis (AS) and VSMC dysfunction remain unknown. In this study, we try to explore the effects of circ_TNPO1 on oxidized low-density lipoprotein (ox-LDL)-induced human vascular smooth muscle cell (VSMC) excessive proliferation and migration, and the potential molecular mechanism.

Methods: Quantitative real-time polymerase chain reaction (RT-qPCR) and western blot experiment were used to detect the serum samples from AS patients and healthy controls. CCK-8, Transwell, and the dual-luciferase reporter gene assay were used to detect the cell biology.

Results: In human AS serum and ox-LDL-induced VSMCs, circ_TNPO1 was increased, whereas miR-181b was decreased. Silencing circ_TNPO1 inhibited proliferation and migration activity and reduced protein expression of PCNA, Ki-67, MMP2, and E-cadherin and promoted N-cadherin protein expression in ox-LDL induced VSMCs. Remarkably, miR-181b knockdown or Notch1 overexpression could efficiently offset the proliferation and migration inhibiting effect of circ_TNPO1 knockdown in ox-LDL-induced VSMCs. Furthermore, a molecular mechanism study pointed out that circ_TNPO1 and Notch1 are direct-acting targets of miR-181b.

Conclusions: In conclusion, our study indicated that circ_TNPO1 promotes the proliferation and migration progression of VSMCs in atherosclerosis through the miR-181b/Notch1 axis.