Profiling neuron-autonomous lncRNA changes upon ischemia/reperfusion injury
Profiling neuron-autonomous lncRNA changes upon ischemia/reperfusion injury
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分析缺血/再灌注损伤时神经元自主 lncRNA 的变化
DOI：
10.1016/j.bbrc.2017.10.157
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发表时间：
2018-01-01
影响因子：
3.1
通讯作者：
Lv, Haitao
中科院分区：
文献类型：
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作者：
Li, Haiying;Wu, Youjia;Lv, Haitao
在缺血性脑卒中后和随后的再灌注过程中，神经元转录组发生广泛的变化。尽管许多研究都关注与缺血性卒中相关的mrna的转录组变化，但对于在细胞稳态中起关键作用的非编码rna （lncRNAs）是否参与这一过程以及多长时间参与这一过程却知之甚少。在本研究中，我们采用高通量筛选的方法，分别在氧葡萄糖剥夺/再灌注（OGD/R）条件下0 h、6 h、12 h和18 h，分析lncRNAs在原培养海马神经元中的表达变化。敲低一个已验证的lncRNAs （Tnxa-ps1）通过抑制细胞凋亡促进神经元存活。编码非编码共表达网络分析显示，Tnxa-ps1的表达与一组特定基因的变化高度相关，其中许多基因与神经保护有关。最后，我们发现Tnxa-ps1的下调逆转了四种mrna在OGD/R后的表达变化，揭示了Tnxa-ps1与选定基因之间的调节作用。总之，我们的数据揭示了lncrna可能参与OGD/R的病理生理，从而为缺血性卒中潜在治疗靶点的研究提供了新的见解。(C) 2017爱思唯尔公司版权所有。
Extensive changes of neuronal transcriptome occur post ischemic stroke and during the following reperfusion. Although numerous studies focused on transcriptome changes of mRNAs associated with ischemic stroke, little is known about whether and how long non-coding RNAs (lncRNAs), which play critical roles in cellular homeostasis, are involved in this process. In this study, we performed high throughput screening to analyze expression changes of lncRNAs in primarily cultured hippocampal neurons under an oxygen-glucose deprivation/reperfusion (OGD/R) condition at 0 h, 6 h, 12 h, and 18 h, respectively. Knock down of one validated lncRNAs (Tnxa-ps1) promoted neuronal survival by inhibiting apoptosis. Coding non-coding co-expression network analysis revealed that the expression of Tnxa-ps1 was highly correlated with changes of a particular group of genes, many of which are associated with neural protection. Finally, we showed that down-regulation of Tnxa-ps1 reversed the expression changes of four mRNAs post OGD/R, revealing a regulatory effect between Tnxa-ps1 and selected genes. Together, our data revealed possible participation of lncRNAs in the pathophysiology of OGD/R and thereby provided new insights into the studies of potential therapeutic targets for ischemic stroke. (C) 2017 Elsevier Inc. All rights reserved.