Abstract

Ischemic stroke (IS) is a common disease that seriously endangers human health. Patients with IS present with increased death of brain microvascular endothelial cells (BMECs). MALAT1 is found to be upregulated in IS patients. However, the function of MALAT1 in IS pathogenesis still remains unclear. This study aimed to investigate the role of MALAT1 in IS in vitro model and the related molecular mechanisms. The expressions of MALAT1 and miR-126 were detected by qPCR. The in vitro IS model was established by treating BMECs with oxygen-glucose deprivation (OGD). Cell viability and cell apoptosis were assessed by MTT assay and flow cytometry, respectively. Luciferase assay was conducted to examine the interplay between MALAT1 and miR-126. Western blotting was used to determine the protein levels of apoptosis-associated proteins (e.g. caspase 3, Bax and Bcl-2) and PI3K/Akt pathway-related proteins (e.g. PI3K, Akt, p-PI3K, p-Akt). OGD induced upregulation of MALAT1 and downregulation of miR-126 in HBMECs. MALAT1 knockdown promoted the proliferation of HBMECs and reduced the proportion of apoptotic HBMECs by regulating the expression of apoptosis-related proteins. MALAT1 targeted and negatively regulated miR-126 expression. Overexpression of miR-126 activated the PI3K/Akt pathway, which in turn affected the proliferation and apoptosis of HBMECs. MALAT1 negatively regulated PI3K/Akt pathway. MALAT1 inhibited the proliferation and induced the apoptosis of OGD-induced HBMECs through suppressing PI3K/AKT pathway by sponging miR-126, providing a potential therapeutic target for IS.

中文翻译：

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LncRNA MALAT1通过海绵miR-126抑制PI3K / Akt信号通路来促进OGD诱导的脑微血管内皮细胞凋亡。

摘要

缺血性中风（IS）是一种严重危害人类健康的常见疾病。IS患者的脑微血管内皮细胞（BMEC）死亡增加。发现IS患者中MALAT1被上调。但是，仍然不清楚MALAT1在IS发病机制中的功能。本研究旨在探讨MALAT1在IS体外模型中的作用及其相关的分子机制。通过qPCR检测MALAT1和miR-126的表达。通过用氧葡萄糖剥夺（OGD）处理BMEC建立体外IS模型。通过MTT测定和流式细胞术分别评估细胞活力和细胞凋亡。进行荧光素酶测定以检查MALAT1和miR-126之间的相互作用。Western印迹法用于确定凋亡相关蛋白（例如半胱天冬酶3，Bax和Bcl-2）和PI3K / Akt途径相关蛋白（例如PI3K，Akt，p-PI3K，p-Akt）。OGD诱导了HBMECs中MALAT1的上调和miR-126的下调。MALAT1敲低促进了HBMECs的增殖，并通过调节凋亡相关蛋白的表达降低了凋亡性HBMECs的比例。MALAT1靶向和负调控的miR-126表达。miR-126的过度表达激活了PI3K / Akt途径，进而影响了HBMEC的增殖和凋亡。MALAT1负调控PI3K / Akt途径。MALAT1通过使miR-126海绵化来抑制PI3K / AKT通路，从而抑制OGD诱导的HBMEC的增殖并诱导其凋亡，为IS提供了潜在的治疗靶点。OGD诱导了HBMECs中MALAT1的上调和miR-126的下调。MALAT1敲低促进了HBMECs的增殖，并通过调节凋亡相关蛋白的表达降低了凋亡性HBMECs的比例。MALAT1靶向和负调控的miR-126表达。miR-126的过度表达激活了PI3K / Akt途径，进而影响了HBMEC的增殖和凋亡。MALAT1负调控PI3K / Akt途径。MALAT1通过使miR-126海绵化来抑制PI3K / AKT通路，从而抑制OGD诱导的HBMEC的增殖并诱导其凋亡，为IS提供了潜在的治疗靶点。OGD诱导了HBMECs中MALAT1的上调和miR-126的下调。MALAT1敲低促进了HBMECs的增殖，并通过调节凋亡相关蛋白的表达降低了凋亡性HBMECs的比例。MALAT1靶向和负调控的miR-126表达。miR-126的过度表达激活了PI3K / Akt途径，进而影响了HBMEC的增殖和凋亡。MALAT1负调控PI3K / Akt途径。MALAT1通过使miR-126海绵化来抑制PI3K / AKT通路，从而抑制OGD诱导的HBMEC的增殖并诱导其凋亡，为IS提供了潜在的治疗靶点。MALAT1靶向和负调控的miR-126表达。miR-126的过度表达激活了PI3K / Akt途径，进而影响了HBMEC的增殖和凋亡。MALAT1负调控PI3K / Akt途径。MALAT1通过使miR-126海绵化来抑制PI3K / AKT途径，从而抑制OGD诱导的HBMEC的增殖并诱导其凋亡，为IS提供了潜在的治疗靶点。MALAT1靶向和负调控的miR-126表达。miR-126的过度表达激活了PI3K / Akt途径，进而影响了HBMEC的增殖和凋亡。MALAT1负调控PI3K / Akt途径。MALAT1通过使miR-126海绵化来抑制PI3K / AKT通路，从而抑制OGD诱导的HBMEC的增殖并诱导其凋亡，为IS提供了潜在的治疗靶点。