Circular RNA circLIFR regulates the proliferation, migration, invasion and apoptosis of human vascular smooth muscle cells via the miR-1299/KDR axis.

Abstract

Dysfunction of vascular smooth muscle cells (VSMCs) plays a critical role in the development of intracranial aneurysm (IA). Here, we explored the detailed role and mechanism of circular RNA (circRNA) LIF receptor subunit alpha (circLIFR, circ_0072309) in human umbilical artery smooth muscle cells (HUASMCs). CircLIFR, microRNA (miR)-1299 and kinase insert domain receptor (KDR) expression levels were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot assays. Cell proliferation was assessed by Cell Counting Kit-8 (CCK-8) and 5-Ethynyl-2'-Deoxyuridine (EdU) assays. Cell migration was gauged by wound-healing and transwell assays. Cell invasion and apoptosis were detected by transwell assay and flow cytometry, respectively. Direct relationship between miR-1299 and circLIFR or KDR was verified by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. CircLIFR and KDR were down-regulated and miR-1299 was up-regulated in the artery wall tissues and ASMCs of IA patients. Enforced expression of circLIFR enhanced HUASMC proliferation, migration, invasion, and impeded apoptosis. Mechanistically, circLIFR directly targeted miR-1299, and miR-1299 was a downstream mediator of circLIFR in regulating the proliferation, migration, invasion and apoptosis of HUASMCs. KDR was identified as a direct and functional target of miR-1299 in HUASMCs. Furthermore, circLIFR was a post-transcriptional regulator of KDR expression through miR-1299. Our findings suggest that circLIFR, an underexpressed circRNA in IA, can regulate the proliferation, migration, invasion and apoptosis of HUASMCs depending on the miR-1299/KDR axis.