Background: The maintenance of human brain microvascular endothelial cell (HBMEC) function is crucial to improve the outcomes of ischemic stroke (IS). Emerging evidence shows that circular RNAs (circRNAs) are involved in IS progression. This study aimed to investigate the role of circRNA FUN14 domain containing 1 (circFUNDC1) in oxygen-glucose deprivation (OGD)-treated HBMECs.
Methods: The expression of circFUNDC1, miR-375 and phosphatase and tensin homolog (PTEN) mRNA was detected by quantitative real-time PCR (qPCR). Cell viability, apoptosis, migration and angiogenesis were determined by CCK-8 assay, flow cytometry assay, transwell assay and tube formation assay. The protein level of PTEN was detected by western blot. The relationship between miR-375 and circFUNDC1 or PTEN was confirmed by pull-down assay, dual-luciferase reporter assay and RIP assay. Exosomes were identified by transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA).
Results: CircFUNDC1 expression was increased in peripheral blood of IS patients and OGD-treated HBMECs. CircFUNDC1 knockdown alleviated OGD-induced cell apoptosis and promoted OGD-blocked cell viability, migration and angiogenesis of HBMECs. MiR-375 was a target of circFUNDC1, and miR-375 restoration played similar effects with circFUNDC1 knockdown. The inhibition of miR-375 reversed the effects of circFUNDC1 knockdown. In addition, PTEN was a downstream target of miR-375, and PTEN overexpression abolished the effects of miR-375 restoration. The expression of circFUNDC1 was elevated in serum-derived exosomes of IS patients, and circFUNDC1 harbored diagnostic values.
Conclusion: CircFUNDC1 knockdown alleviates OGD-induced HBMECs injuries by inhibiting PTEN via enriching miR-375.
Keywords: HBMEC; Ischemic stroke; PTEN; circFUNDC1; miR-375.
Copyright © 2021. Published by Elsevier B.V.