OBJECTIVE Apoptosis is a prominent form of neuron death in cerebral ischemia-reperfusion-induced injury. Accompanied with the pathogenesis, Circ_002664 is upregulated. However, its role in the neuron apoptosis and the underlying mechanisms are unknown. METHODS In this study, HT22 cells were treated with oxygen glucose deprivation and reoxygenation (OGD/R). The cell viability, apoptosis, proliferation and mitochondrial potential were examined. The expressions of interested genes, Circ_002664, miR-182-5p and Herpud1, were measured. The roles of these genes in OGD/R-induced cell injury were investigated by knockdown, overexpression alone or in combination. Additionally, the interactions between Circ_002664, miR-182-5p and Herpud1 were validated by luciferase report assay. The levels of MAP2, CHOP, Cytochrome C (CYC) and cleaved caspase-3 were determined. RESULTS OGD/R treatment significantly increased cell apoptosis, decreased cell proliferation and mitochondrial potential, as well as increased Circ_002664 and Herpud1 expressions, and decreased miR-182-5p level. Circ_002664 knockdown markedly inhibited the effects by OGD/R on cell survival and altered expression of miR-182-5p and Herpud1. MiR-182-5p was observed sponged by Circ_002664 and negatively mediated its effect above mentioned, and this was by directly targeting Herpud1. Additionally, it was observed that CHOP expressions were regulated by Circ_002664/miR-182-5p/Herpud1 pathway, and in turn mediated its regulation in CYC and cleaved caspase-3. CONCLUSIONS In summary, our data showed that the Circ_002664 importantly contributed to neuronal cell apoptosis induced by OGD/R treatment, and this might be achieved by directly targeting miR-182-5p/Herpud1 pathway.

中文翻译：

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Circ_002664 / miR-182-5p / Herpud1通路对OGD / R诱导的神经元细胞凋亡起重要作用。

目的凋亡是脑缺血再灌注所致损伤中神经元死亡的主要形式。伴随发病机理，Circ_002664被上调。然而，其在神经元凋亡和潜在机制中的作用尚不清楚。方法在这项研究中，对HT22细胞进行了氧葡萄糖剥夺和复氧（OGD / R）处理。检查细胞活力，凋亡，增殖和线粒体电位。测量了感兴趣的基因Circ_002664，miR-182-5p和Herpud1的表达。这些基因在OGD / R诱导的细胞损伤中的作用已通过敲低，单独或联合表达来研究。此外，通过荧光素酶报告检测验证了Circ_002664，miR-182-5p和Herpud1之间的相互作用。MAP2，CHOP，确定了细胞色素C（CYC）和裂解的caspase-3。结果OGD / R处理可显着增加细胞凋亡，降低细胞增殖和线粒体潜能，并提高Circ_002664和Herpud1表达，并降低miR-182-5p水平。Circ_002664敲低明显抑制了OGD / R对细胞存活的影响，并改变了miR-182-5p和Herpud1的表达。Circ_002664发现MiR-182-5p呈海绵状，并负面地介导了上述效应，这是通过直接靶向Herpud1来实现的。此外，观察到CHOP表达受Circ_002664 / miR-182-5p / Herpud1途径调控，并进而介导其在CYC和裂解caspase-3中的调控。结论总之，我们的数据表明Circ_002664对OGD / R处理诱导的神经元细胞凋亡具有重要作用，