Long non-coding RNA MALAT1 was previously revealed to express abnormally in animal and cellular models of stroke, suggesting its indispensable role in stroke. The aims of the present study were to further investigate the functions of MALAT1 and to elucidate the underlying molecular mechanisms. Oxygen glucose deprivation/re-oxygenation (OGD/R) challenge was used in human brain microvascular endothelial cells (HBMECs) to mimic stroke injury in vitro. MALAT1 and miR-205-5p expression levels were evaluated by qRT-PCR. A tube formation assay was employed to verify the angiogenesis of HBMECs. Cell proliferation and apoptosis were evaluated using the ErdU assay and flow cytometry analysis, respectively. The interaction between miR-205-5p and MALAT1 was verified by dual-luciferase reporter assay. MALAT1 and miR-205-5p were both significantly upregulated in the serum of CIS patients and HBMECs under OGD/R, and the tube formation of HBMECs was damaged after OGD/R treatment. Silencing miR-205-5p remarkably promoted HBMEC proliferation and angiogenesis to resist OGD/R injury. Knockdown of MALAT1 markedly inhibited HBMEC proliferation and angiogenesis, and meanwhile promoted apoptosis induced by OGD/R treatment. Most importantly, MALAT1 acted as a competing endogenous RNA (ceRNA) of miR-205-5p via direct bonding with each other in HBMECs under OGD/R damage, indirectly upregulating the downstream targeted gene VEGFA. MALAT1 protected the angiogenesis function of HBMECs under OGD/R conditions by interacting with miR-205-5p/VEGFA pathway.

中文翻译：

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MALAT1通过与miR-205-5p / VEGFA途径相互作用，在氧葡萄糖剥夺/再充氧（OGD / R）挑战下保护人脑微血管内皮细胞（HBMEC）的血管生成功能。

先前发现长非编码RNA MALAT1在中风的动物和细胞模型中异常表达，表明其在中风中不可或缺。本研究的目的是进一步研究MALAT1的功能并阐明潜在的分子机制。在人脑微血管内皮细胞（HBMEC）中使用了氧葡萄糖剥夺/再氧合（OGD / R）挑战模拟体外中风损伤。通过qRT-PCR评估MALAT1和miR-205-5p的表达水平。使用管形成测定法来验证HBMEC的血管生成。分别使用ErdU分析和流式细胞仪分析评估细胞增殖和凋亡。miR-205-5p和MALAT1之间的相互作用已通过双萤光素酶报告基因检测得以证实。在OGD / R下，CIS患者和HBMECs的血清中MALAT1和miR-205-5p均显着上调，在OGD / R处理后，HBMEC的管形成受到破坏。沉默miR-205-5p可显着促进HBMEC增殖和血管生成，从而抵抗OGD / R损伤。敲除MALAT1可以显着抑制HBMEC增殖和血管生成，并同时促进OGD / R处理诱导的细胞凋亡。最重要的是，MALAT1在OGD / R损伤下通过在HBMEC中彼此直接键合而充当miR-205-5p的竞争内源RNA（ceRNA），间接上调下游靶向基因VEGFA。MALAT1通过与miR-205-5p / VEGFA途径相互作用，在OGD / R条件下保护了HBMEC的血管生成功能。OGD / R处理后，HBMECs的管形成受到破坏。沉默miR-205-5p可显着促进HBMEC增殖和血管生成，从而抵抗OGD / R损伤。敲低MALAT1明显抑制HBMEC增殖和血管生成，同时促进OGD / R处理诱导的细胞凋亡。最重要的是，MALAT1在OGD / R损伤下通过在HBMEC中彼此直接键合而充当miR-205-5p的竞争内源RNA（ceRNA），间接上调下游靶向基因VEGFA。MALAT1通过与miR-205-5p / VEGFA途径相互作用，在OGD / R条件下保护了HBMEC的血管生成功能。OGD / R处理后，HBMECs的管形成受到破坏。沉默miR-205-5p可显着促进HBMEC增殖和血管生成，从而抵抗OGD / R损伤。敲低MALAT1明显抑制HBMEC增殖和血管生成，同时促进OGD / R处理诱导的细胞凋亡。最重要的是，MALAT1在OGD / R损伤下通过在HBMEC中彼此直接键合而充当miR-205-5p的竞争内源RNA（ceRNA），间接上调下游靶向基因VEGFA。MALAT1通过与miR-205-5p / VEGFA途径相互作用，在OGD / R条件下保护了HBMEC的血管生成功能。同时促进了OGD / R处理诱导的细胞凋亡。最重要的是，MALAT1在OGD / R损伤下通过在HBMEC中彼此直接键合而充当miR-205-5p的竞争内源RNA（ceRNA），间接上调下游靶向基因VEGFA。MALAT1通过与miR-205-5p / VEGFA途径相互作用，在OGD / R条件下保护了HBMEC的血管生成功能。同时促进了OGD / R处理诱导的细胞凋亡。最重要的是，MALAT1在OGD / R损伤下通过在HBMEC中彼此直接键合而充当miR-205-5p的竞争内源RNA（ceRNA），间接上调下游靶向基因VEGFA。MALAT1通过与miR-205-5p / VEGFA途径相互作用，在OGD / R条件下保护了HBMEC的血管生成功能。