LncRNA NEAT1 facilitates survival and angiogenesis in oxygen-glucose deprivation (OGD)-induced brain microvascular endothelial cells (BMECs) via targeting miR-377 and upregulating SIRT1, VEGFA, and BCL-XL.
Brain Res
; 1707: 90-98, 2019 03 15.
Article
em En
| MEDLINE
| ID: mdl-30408478
ABSTRACT
OBJECTIVE:
The present study was designed to investigate the mechanism by which lncRNA NEAT1 regulates survival and angiogenesis in oxygen-glucose deprivation (OGD)-induced brain microvascular endothelial cells (BMECs).METHODS:
OGD-treated BMECs were used to mimic cerebral ischaemia in vitro. The expression of lncRNA NEAT1 and miR-377 and proteins including VEGFA, SIRT1, and BCL-XL were measured by real-time quantitative PCR (qRT-PCR) and western blot, respectively. Cell viability and caspase 3 activity of BMECs under different conditions were determined using MTT and caspase activity assays, respectively. Matrigel-based angiogenesis assays were employed to evaluate the effect of lncRNA NEAT1 on angiogenesis. A dual-luciferase reporter assay was used to validate direct binding of miR-377 to putative targets.RESULTS:
OGD exposure reduced the cell viability of BMECs. Upregulation of lncRNA NEAT1 and downregulation of miR-377 were also observed under OGD conditions. Knockdown of lncRNA NEAT1 inhibited angiogenesis and aggravated apoptosis in OGD-induced BMECs. Meanwhile, the expression level of miR-377 was upregulated while its downstream targets (VEGFA, SIRT1, and BCL-XL) were downregulated after lncRNA NEAT1 knockdown. Furthermore, miR-377 inhibited the angiogenesis and survival of OGD-induced BMECs. The expression of VEGFA, SIRT1, and BCL-XL were all attenuated by miR-377 overexpression. The dual-luciferase reporter assay proved miR-377 targeted the 3' UTR sequences of lncRNA NEAT1, VEGFA, SIRT1, and BCL-XL.CONCLUSION:
lncRNA NEAT1 facilitated the survival and angiogenesis of OGD-induced BMECs via targeting miR-377 and promoting the expression of VEGFA, SIRT1, and BCL-XL, suggesting that lncRNA NEAT1 could be a promising target for cerebral ischaemia treatment.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Encéfalo
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Isquemia Encefálica
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MicroRNAs
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Células Endoteliais
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Fator A de Crescimento do Endotélio Vascular
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Proteína bcl-X
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RNA Longo não Codificante
Limite:
Animals
Idioma:
En
Revista:
Brain Res
Ano de publicação:
2019
Tipo de documento:
Article