Chao Liu1, Xiaohui Xu2, Chao Huang2, Li Zhang2, Dandan Shang2, Weiwei Cai2, Yupeng Wang2. 1. Department of Neurology, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, Henan, 471000, China. Electronic address: liuchao-20001103@163.com. 2. Department of Neurology, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, Henan, 471000, China.
Abstract
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.
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.