Long non-coding RNA H19 contributes to apoptosis of hippocampal neurons by inhibiting let-7b in a rat model of temporal lobe epilepsy.
Long non-coding RNA H19 contributes to apoptosis of hippocampal neurons by inhibiting let-7b in a rat model of temporal lobe epilepsy.
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长链非编码 RNA H19 通过抑制颞叶癫痫大鼠模型中的 let-7b 促进海马神经元凋亡
DOI：
10.1038/s41419-018-0496-y
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发表时间：
2018-05-23
影响因子：
9
通讯作者：
Meng FG
中科院分区：
文献类型：
--
作者：
Han CL;Ge M;Liu YP;Zhao XM;Wang KL;Chen N;Hu W;Zhang JG;Li L;Meng FG
颞叶癫痫(TLE)是最常见的顽固性癫痫类型之一，以海马神经元损伤和海马硬化为特征。长非编码RNA(LncRNAs)作为转录后调控因子已被越来越多地认识到。然而，它们在TLE中的表达水平和功能在很大程度上仍不清楚。本研究以TLE大鼠为模型，采用基因芯片技术研究癫痫大鼠海马区LncRNAs的表达谱。我们的结果表明，H19是分化最明显的lncRNA，在TLE潜伏期显著上调。此外，采用功能获得和功能丧失的体内研究表明，H19的过度表达加剧了SE诱导的海马神经元凋亡，而抑制H19对SE诱导的细胞损伤具有保护作用。最后，我们证明了H19在细胞凋亡的调节中可能作为一个竞争的内源RNA来海绵microRNA let-7b。总之，我们的研究揭示了lncRNA H19在癫痫诱导的神经损伤中的一种新的机制，并为开发基于lncRNA的策略以减少癫痫诱导的脑损伤提供了新的靶点。
Temporal lobe epilepsy (TLE) is one of the most common types of intractable epilepsy, characterized by hippocampal neuron damage and hippocampal sclerosis. Long noncoding RNAs (lncRNAs) have been increasingly recognized as posttranscriptional regulators. However, their expression levels and functions in TLE remain largely unknown. In the present study, TLE rat model is used to explore the expression profiles of lncRNAs in the hippocampus of epileptic rats using microarray analysis. Our results demonstrate that H19 is the most pronouncedly differentiated lncRNA, significantly upregulated in the latent period of TLE. Moreover, the in vivo studies using gain- and loss-of-function approaches reveal that the overexpression of H19 aggravates SE-induced neuron apoptosis in the hippocampus, while inhibition of H19 protects the rats from SE-induced cellular injury. Finally, we show that H19 might function as a competing endogenous RNA to sponge microRNA let-7b in the regulation of cellular apoptosis. Overall, our study reveals a novel lncRNA H19-mediated mechanism in seizure-induced neural damage and provides a new target in developing lncRNA-based strategies to reduce seizure-induced brain injury.
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影响因子：
11.2
作者：
Helmstaedter, C;Kurthen, M;Elger, CE
通讯作者：
Elger, CE
影响因子：
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TYCKO, B
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作者：
Kapranov, Philipp;Cheng, Jill;Gingeras, Thomas R.
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