Hsa_circ_0000285-Mediated miR-599/RGS17 Axis Participates in the Pathogenesis of Abdominal Aortic Aneurysm by Regulating the Functions of Vascular Smooth Muscle Cells

Objective: Abdominal aortic aneurysm (AAA) is characterized by vascular smooth muscle cell (VSMC) injury. Circ_0000285 has been declared to drive cancer development, but its role in AAA remains unclear. We thus intended to disclose circ_0000285's role and molecular mechanism in AAA.

Methods: VSMCs were exposed to hydrogen peroxide (H₂O₂) to induce cell injury. Circ_0000285, miR-599, and regulator of G protein signaling 17 (RGS17) mRNA expressions were ascertained by conducting RT-qPCR assay while the levels of RGS17 protein was ascertained via western blotting. MiR-599's predicted binding with circ_0000285 and RGS17 were validated by means of the dual-luciferase reporter experiment. Cell proliferation was evaluated through the CCK-8 and EdU assays. Cell apoptosis was assessed via the caspase-3 activity assay.

Results: The AAA samples and H₂O₂-treated VSMCs manifested high expressions of circ_0000285 and RGS17 as well as a poor miR-599 expression. H₂O₂ treatment impaired the proliferation of VSMCs while stimulating their apoptosis. Circ_0000285 overexpression further repressed cell proliferation and enhanced apoptosis in H₂O₂-treated VSMCs while miR-599 enrichment partly reversed these effects. Circ_0000285 directly bound to miR-599, and miR-599 interacted with RGS17 3'UTR. RGS17 overexpression also suppressed cell proliferation and stimulated apoptosis in H₂O₂-treated VSMCs. Nevertheless, these effects were offset by miR-599 enrichment.

Conclusion: Circ_0000285 governed the miR-599/RGS17 network to regulate H₂O₂-induced VSMC injuries, thereby promoting the development of AAA.