The pivotal regulatory role of circular RNAs (circRNAs) in ischemic stroke (IS) has been expounded. The study aimed to probe the exact role and underlying mechanism of circVRK1 in oxygen-glucose deprivation (OGD)-induced human brain microvascular endothelial cells (HBMECs) injury. HBMECs challenged by OGD were used as in vitro models of IS. Quantitative real-time PCR was used to examine the levels of circVRK1, vaccinia-related kinase 1 (VRK1), miR-150-5p and MLLT1 mRNA. Cell viability, migration angiogenesis ability and death were evaluated by Cell counting kit-8 assay, transwell assay, wound-healing assay, tube formation assay and flow cytometry analysis. All the protein levels were monitored by western blot assay. Enzyme-linked immunosorbent assay was conducted for examining cell oxidative stress. Dual-luciferase reporter assay, RIP assay and RNA pull-down assay were performed to verify the combination between miR-150-5p and circVRK1 or MLLT1. CircVRK1 was upregulated in OGD-treated HBMECs. CircVRK1 knockdown alleviated OGD-caused effects on HBMECs migration, angiogenesis, death, inflammatory response and oxidative stress. Furthermore, circVRK1 could sponge miR-150-5p, and miR-150-5p silencing also mitigated the impact of circVRK1 deficiency on OGD-evoked injury. Besides, MLLT1 acted as a molecular target of miR-150-5p, and the protective influence of miR-150-5p on OGD-induced cell damage was overturned by MLLT1 introduction. CircVRK1 knockdown weakened OGD-evoked injury in HBMECs through modulating miR-150-5p/MLLT1 pathway, and this might supply new insights and probable targets for IS treatment.
Keywords: Circvrk1; HBMECs; Ischemic stroke; MLLT1; miR-150-5p.
© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.