LncRNA MIAT overexpression reduced neuron apoptosis in a neonatal rat model of hypoxic-ischemic injury through miR-211/GDNF
LncRNA MIAT overexpression reduced neuron apoptosis in a neonatal rat model of hypoxic-ischemic injury through miR-211/GDNF
复制标题
DOI：
10.1080/15384101.2018.1560202
复制
发表时间：
2019-01-17
期刊：
影响因子：
4.3
通讯作者：
Wu, Hong
中科院分区：
文献类型：
--
作者：
Li, En-yao;Zhao, Peng-ju;Wu, Hong
目的：目的探讨心肌梗死相关基因（MIAT）在新生儿缺氧缺血性脑性瘫痪发病中的作用机制。材料与方法：建立新生大鼠HI损伤模型，检测其运动功能。通过qRT-PCR或western blot检测LncRNA MIAT、miR-211、胶质细胞系源性神经营养因子（GDNF）和caspase-3的表达。流式细胞仪检测细胞凋亡情况。进行RNA免疫沉淀（RIP）和RNA下拉测定以确认MIAT和miR-211之间的相互作用。结果如下：与对照组相比，HI组和OGD诱导的Neuro 2A细胞缺血损伤时，lncRNA MIAT和GDNF表达下调，而miR-211表达上调。lncRNA MIAT与miR-211相互作用，lncRNA MIAT过表达通过miR-211减少神经元凋亡。此外，在Neuro 2A细胞中，GDNF的表达受lncRNA MIAT的正调控，受miR-211的负调控。在体实验证明MIAT能促进运动功能，减轻HI损伤。结论：MIAT过表达可通过miR-211/GDNF减少Neuro 2A细胞凋亡，减轻新生大鼠HI损伤。
Objective: To investigate the underlying mechanism of lncRNA myocardial infarction-associated transcript (MIAT) in hypoxic-ischemic (HI)-induced neonatal cerebral palsy. Materials and methods: Neonatal rat model of HI injury was established to detect the motor function. LncRNA MIAT, miR-211, glial cell line-derived neurotrophic factor (GDNF) and caspase-3 expressions were measured by qRT-PCR or western blot. The apoptosis of Neuro2A cells was detected by flow cytometry. RNA immunoprecipitation (RIP) and RNA pull-down assays were performed to confirm the interaction between MIAT and miR-211. Results: Compared with control group, lncRNA MIAT and GDNF were downregulated in striatal tissues of neonatal rats in HI group and oxygen glucose deprivation (OGD)-induced ischemic injury of Neuro2A cells, whereas miR-211 was up-regulated in striatal tissues of HI group and OGD-induced ischemic injury of Neuro2A cells. LncRNA MIAT interacted with miR-211, and lncRNA MIAT overexpression reduced neuron apoptosis through miR-211. Besides, GDNF expression was positively regulated by lncRNA MIAT and negatively regulated by miR-211 in Neuro2A cells. In vivo experiment proved MIAT promoted motor function and relieved HI injury. Conclusion: MIAT overexpression reduced apoptosis of Neuro2A cells through miR-211/GDNF, which relieved HI injury of neonatal rats.