Background: Dysfunction of endothelial cells in the arterial vasculature is an essential contributor to the pathogenesis of atherosclerosis. Circular RNAs (circRNAs) exert important regulatory functions in endothelial cell dysfunction. Here, we explored the precise role and mechanism of circ_0050486 in regulating endothelial cell injury induced by oxidized low-density lipoprotein (ox-LDL).
Methods: Circ_0050486, microRNA (miR)-182-5p and myeloid differentiation primary response gene 88 (MyD88) were quantified by quantitative real-time PCR or western blot. Cell viability, proliferation and apoptosis were examined by MTS, 5-Ethynyl-2'-Deoxyuridine (EdU), and flow cytometry assays, respectively. Direct relationship between miR-182-5p and circ_0050486 or MYD88 was verified by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays.
Results: Circ_0050486 was upregulated in atherosclerosis serum and ox-LDL-treated human aortic endothelial cells (HAECs). Silencing of circ_0050486 suppressed HAEC injury induced by ox-LDL. Mechanistically, circ_0050486 targeted miR-182-5p, and the effects of circ_0050486 silencing were partially due to the upregulation of miR-182-5p. MYD88 was a direct target of miR-182-5p, and miR-182-5p-mediated inhibition of MYD88 attenuated ox-LDL-evoked HAEC injury. Circ_0050486 bound to miR-182-5p to regulate MYD88 expression. Additionally, the NF-κB signaling pathway was involved in the regulation of circ_0050486/miR-182-5p/MYD88 axis in ox-LDL-treated HAECs.
Conclusion: Our study identifies the functional role of circ_0050486 in ox-LDL-induced endogenous cell injury and establishes a mechanism of circ_0050486 function by affecting MYD88 through competitively binding to shared miR-182-5p.
Keywords: Atherosclerosis; MYD88; circ_0050486; endogenous cells; miR-182-5p.