Blockage of miR-485-5p on Cortical Neuronal Apoptosis Induced by Oxygen and Glucose Deprivation/Reoxygenation Through Inactivating MAPK Pathway

被引:6
|
作者
Yin, Jiangliu [1 ]
Chen, Huan [2 ]
Li, Suonan [1 ]
Zhang, Shuai [1 ]
Guo, Xieli [3 ]
机构
[1] Univ South China, Changsha Cent Hosp, Dept Neurosurg, Changsha 410005, Hunan, Peoples R China
[2] Hunan Prov Ctr Dis Prevent & Control, Changsha 410006, Hunan, Peoples R China
[3] Quanzhou Med Coll, Jinjiang Municipal Hosp, Dept Neurosurg, 392 Xinhua Rd,Meiling St, Quanzhou 362200, Fujian, Peoples R China
关键词
miR-485-5p; SOX6; Oxygen and glucose deprivation; reoxygenation; Apoptosis; Lactate dehydrogenase; RN-c; PROLIFERATION; MICRORNA; INJURY; CELLS;
D O I
10.1007/s12017-020-08605-3
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
This study is designed to explore the role of miR-485-5p in hypoxia/reoxygenation-induced neuronal injury in primary rat cortical neurons. Hypoxia/reoxygenation model was established through oxygen and glucose deprivation/reoxygenation (OGD/R). RN-c cells were transfected with miR-485-5p mimics, miR-485-5p inhibitors, si-SOX6, pCNDA3.1-SOX6 or miR-485-5p + pCDNA3.1-SOX6, in which cell viability, apoptosis, lactate dehydrogenase (LDH) release rate were assessed. Western blot detected the protein expressions of apoptotic-related proteins (caspase3, Bcl-2, Bax) and the phosphorylated level of ERK1/2. The potential binding sites between miR-485-5p and SOX6 were predicted by STARBASE and identified using dual luciferase reporter gene assay. OGD/R-treated RN-c cell presented increases in apoptosis and LDH release rate as well as a decrease in cell viability. miR-485-5p was downregulated while SOX6 was upregulated in OGD/R-treated RN-c cells. Overexpression of miR-485-5p or SOX6 knockdown rescued cell viability and Bcl-2 expression, while attenuated apoptosis, LDH release rate, expression of SOX6 and the phosphorylated level of ERK1/2. Consistently, miR-485-5p inhibition led to the reverse pattern. Co-transfection of miR-485-5p and SOX6 reversed the protective effect of miR-485-5p on OGD/R-induced neuronal apoptosis. miR-485-5p can directly target SOX6. Together, miR-485-5p inhibited SOX6 to alleviate OGD/R-induced apoptosis. Collectively, miR-485-5p protects primary cortical neurons against hypoxia injury through downregulating SOX6 and inhibiting MAPK pathway.
引用
收藏
页码:256 / 266
页数:11
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