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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

•lncRNA NEAT1 protects BMEC from OGD induced injury.•lncRNA NEAT1 facilitates angiogenesis in OGD induced BMEC.•lncRNA exhibits protective effect via targeting miR-377 and uprelating VEGFA, SIRT1, BCL-XL. The present study was designed to investigate the mechanism by which lncRNA NEAT1 regulates sur...

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Published in:Brain research 2019-03, Vol.1707, p.90-98
Main Authors: Zhou, Zhi-Wen, Zheng, Li-Jun, Ren, Xiang, Li, Ai-Ping, Zhou, Wen-Sheng
Format: Article
Language:English
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Summary:•lncRNA NEAT1 protects BMEC from OGD induced injury.•lncRNA NEAT1 facilitates angiogenesis in OGD induced BMEC.•lncRNA exhibits protective effect via targeting miR-377 and uprelating VEGFA, SIRT1, BCL-XL. 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). 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. 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. 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.
ISSN:0006-8993
1872-6240
DOI:10.1016/j.brainres.2018.10.031