Ischemia stroke is one of the leading causes of death and disability in the world. Long non-coding RNA ANRIL has been reported to play an important role in ischemic injury. In this study, we aim to explore the mechanism by which ANRIL exhibits protective effect. Middle cerebral artery occlusion mouse models were applied and infarction areas were assessed by TTC assay. The expression of ANRIL and miR-199a-5p were determined by qPCR. Oxygen and glucose deprivation treatment was applied to mimic in vitro ischemia injury in N-2a cells. The levels of BCL-2, BAX, MEK, ERK, CAV-1 were determined by western blot. Cell viability were assessed by MTT assay. The direct interaction among miR-199a-5p and ANRIL, miR-199a-5p and CAV-1 were demonstrated by dual Luciferase report assay. ANRIL and miR-199a-5p expression were changed in both in vivo and in vitro ischemia model. Overexpression of ANRIL or inhibition of miR-199a-5p could protect cells against ischemia induced injury by elevating cell viability through CAV-1 mediated MEK/ERK pathway. miR-199a-5p attenuated CAV-1 expression by direct targeting. ANRIL competitively interacted with miR-199a-5p in N-2a cells, leading to a de-repression of CAV-1. ANRIL protects N-2a cells against ischemia induced injury by elevated CAV-1 by competitively interacting with miR-199a-5p, thus activating MEK/ERK pathway and elevating cell viability.

中文翻译：

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lncRNA ANRIL通过miR-199a-5p / CAV-1轴改善了神经元细胞中的氧气和葡萄糖剥夺（OGD）诱导的损伤。

缺血性中风是世界上导致死亡和残疾的主要原因之一。据报道，长的非编码RNA ANRIL在缺血性损伤中起重要作用。在这项研究中，我们旨在探讨ANRIL发挥保护作用的机制。应用大脑中动脉闭塞小鼠模型并通过TTC测定评估梗塞面积。通过qPCR确定ANRIL和miR-199a-5p的表达。氧和葡萄糖剥夺治疗被用于模拟N-2a细胞的体外缺血损伤。通过蛋白质印迹法测定BCL-2，BAX，MEK，ERK，CAV-1的水平。通过MTT测定评估细胞活力。miR-199a-5p和ANRIL，miR-199a-5p和CAV-1之间的直接相互作用已通过双重萤光素酶报告检测得以证实。在体内和体外缺血模型中，ANRIL和miR-199a-5p的表达均发生变化。ANRIL的过表达或miR-199a-5p的抑制可通过通过CAV-1介导的MEK / ERK途径提高细胞活力来保护细胞免受缺血诱导的损伤。miR-199a-5p通过直接靶向减弱了CAV-1的表达。ANRIL在N-2a细胞中与miR-199a-5p竞争性相互作用，导致CAV-1的抑制。ANRIL通过与miR-199a-5p竞争性相互作用保护N-2a细胞免受CAV-1升高引起的缺血性损伤，从而激活MEK / ERK途径并提高细胞活力。ANRIL在N-2a细胞中与miR-199a-5p竞争性相互作用，导致CAV-1的抑制。ANRIL通过与miR-199a-5p竞争性相互作用保护N-2a细胞免受CAV-1升高引起的缺血性损伤，从而激活MEK / ERK途径并提高细胞活力。ANRIL在N-2a细胞中与miR-199a-5p竞争性相互作用，导致CAV-1的抑制。ANRIL通过与miR-199a-5p竞争性相互作用保护N-2a细胞免受CAV-1升高引起的缺血性损伤，从而激活MEK / ERK途径并提高细胞活力。