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.
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The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
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The present study was supported by Key Natural Science Projects of Universities in Anhui Province (No. KJ2020A0970) and Young Talents Support Project in Anhui Provin- ce China (No. gxyqZD2020065).
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Zhang, H., Zhang, B., Chen, C. et al. Circular RNA circLIFR regulates the proliferation, migration, invasion and apoptosis of human vascular smooth muscle cells via the miR-1299/KDR axis. Metab Brain Dis (2021). https://doi.org/10.1007/s11011-021-00853-x
- Intracranial aneurysm