LncRNA DANCR attenuates brain microvascular endothelial cell damage induced by oxygen-glucose deprivation through regulating of miR-33a-5p/XBP1s
LncRNA DANCR attenuates brain microvascular endothelial cell damage induced by oxygen-glucose deprivation through regulating of miR-33a-5p/XBP1s
复制标题
DOI：
10.18632/aging.102712
复制
发表时间：
2020-01-31
期刊：
影响因子：
5.2
通讯作者：
Xiao, Bo
中科院分区：
文献类型：
--
作者：
Zhang, Mengqi;Tang, Mimi;Xiao, Bo
缺血性卒中后脑微血管内皮细胞(BMEC)的存活和血管生成对改善卒中预后具有重要意义。IncRNAs的异常变异与中风密切相关。本研究探讨分化拮抗非蛋白编码RNA(DANCR)对缺氧缺糖(OGD)诱导的BMECs的凋亡、迁移和血管生成的影响及其分子机制。我们发现，在OGD后2、4、6、8和10h，DANCR的表达显著增加。DANCR过表达促进了OGD处理的BMECs的细胞活力、迁移和血管生成。此外，我们还发现X-box结合蛋白I剪接(XBP1s)的表达与DANCR的表达呈正相关。DANCR过表达促进了OGD处理的BMEC中XBP1s的表达。在OGD处理的BMEC中，沉默的XBP1逆转了DANCR的作用。此外，我们还发现microRNA(MiR)-33a-5p与DANCR和XBP1的3‘-UTR结合。MIR-33a-5p过表达抑制了OGD处理后DANCR过表达的BMECs的增殖、迁移、血管生成和XBP1s的表达，从而逆转了DANCR的保护作用。最后，我们发现XBP1s的表达促进了细胞的增殖、迁移和血管生成，逆转了miR-33a-5p的损伤作用。总之，DANCR通过miR-33a-5p/XEMS轴促进了OGD处理的BMECs的存活和血管生成。
Brain microvascular endothelial cell (BMEC) survival and angiogenesis after ischemic stroke has great significance for improving the prognosis of stroke. Abnormal variants of IncRNAs are closely associated with stroke. In this study, we examined the effects and molecular mechanisms of differentiation antagonizing non-protein coding RNA (DANCR) on apoptosis, migration, and angiogenesis of oxygen-glucose deprivation (OGD)-treated BMECs. We found that DANCR expression significantly increased at 2, 4, 6, 8, and 10 h after OGD. DANCR overexpression promoted cell viability, migration, and angiogenesis in OGD-treated BMECs. Additionally, we found that X-box binding protein I splicing (XBP1s) expression was positively correlated with DANCR expression. DANCR overexpression promoted XBP1s expression in OGD-treated BMECs. Silenced XBP1s reversed the effect of DANCR in OGD-treated BMECs. Furthermore, we found that microRNA (miR)-33a-5p bound to DANCR and the 3'-UTR of XBP1. miR-33a-5p overexpression inhibited proliferation, migration, angiogenesis, and XBP1s expression in OGD-treated DANCR-overexpressing BMECs, reversing the protective effect of DANCR. Finally, we found that XBP1s expression promoted proliferation, migration, and angiogenesis, reversing the damaging effect of miR-33a-5p. In conclusion, DANCR enhanced survival and angiogenesis in OGD-treated BMECs through the miR-33a-5p/xems axis.