Abstract | 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.
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Authors | Xiumei Bai, Xi Liu, Haixia Wu, Jiaqing Feng, Hua Chen, Diangui Zhou |
Journal | Neuroscience letters
(Neurosci Lett)
Vol. 770
Pg. 136381
(01 23 2022)
ISSN: 1872-7972 [Electronic] Ireland |
PMID | 34906568
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2021. Published by Elsevier B.V. |
Chemical References |
- FUNDC1 protein, human
- MIRN375 microRNA, human
- Membrane Proteins
- MicroRNAs
- Mitochondrial Proteins
- RNA, Circular
- PTEN Phosphohydrolase
- PTEN protein, human
- Glucose
- Oxygen
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Topics |
- Aged
- Brain
(blood supply)
- Cell Hypoxia
- Cells, Cultured
- Endothelial Cells
(metabolism)
- Endothelium, Vascular
(cytology, metabolism)
- Exosomes
(metabolism)
- Female
- Glucose
(deficiency)
- Humans
- Ischemic Stroke
(genetics, metabolism)
- Male
- Membrane Proteins
(genetics)
- MicroRNAs
(genetics, metabolism)
- Microvessels
(cytology, metabolism)
- Middle Aged
- Mitochondrial Proteins
(genetics)
- Oxygen
(metabolism)
- PTEN Phosphohydrolase
(genetics, metabolism)
- RNA, Circular
(genetics, metabolism)
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