Han Chun-Lei, Liu Yun-Peng, Zhao Xue-Min, Wang Kai-Liang, Chen Ning, Hu Wei, Zhang Jian-Guo, Ge Ming, Meng Fan-Gang
Department of Functional Neurosurgery, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China; Beijing Key Laboratory of Neuromodulation, Beijing Municipal Science and Technology Commission, Beijing 100050, China.
Beijing Key Laboratory of Neuromodulation, Beijing Municipal Science and Technology Commission, Beijing 100050, China; Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
Biochem Biophys Res Commun. 2017 Jul 22;489(2):262-269. doi: 10.1016/j.bbrc.2017.05.161. Epub 2017 May 28.
Understanding the molecular mechanisms mediating epileptogenesis may lead to the development of preventative therapies against epilepsy. Our previous study demonstrated that the long non-coding RNA H19 contributes to epileptogenesis by aggravating status epilepticus-induced neuronal loss, glial cell activation, mossy fiber sprouting, and cognitive impairments in epileptic rats. However, the systematic functions and downstream targets of H19 associated with epileptogenesis are still unknown. In the present study, high-throughput microarray analysis was used to explore the influence of H19 on gene expression in an epileptic rat model. A large number of genes were differentially expressed at the transcriptional level when H19 was overexpressed or knocked down. Series test of cluster analysis further distinguished genes associated with H19. Function and pathway analyses demonstrated that H19 has diverse functions related to epileptogenesis, including demyelination, immune and inflammatory responses, cell apoptosis, and activation of MAPK. This study implicates H19 in a broad spectrum of epileptogenic processes, thereby providing a range of targets for further mechanistic investigations.
了解介导癫痫发生的分子机制可能会推动抗癫痫预防性疗法的发展。我们之前的研究表明，长链非编码RNA H19通过加重癫痫持续状态诱导的癫痫大鼠神经元丢失、胶质细胞激活、苔藓纤维出芽和认知障碍，促进癫痫发生。然而，与癫痫发生相关的H19的系统功能和下游靶点仍然未知。在本研究中，采用高通量微阵列分析来探究H19对癫痫大鼠模型基因表达的影响。当H19过表达或敲低时，大量基因在转录水平上差异表达。聚类分析的系列检验进一步区分了与H19相关的基因。功能和通路分析表明，H19具有与癫痫发生相关的多种功能，包括脱髓鞘、免疫和炎症反应、细胞凋亡以及丝裂原活化蛋白激酶（MAPK）的激活。本研究表明H19参与了广泛的癫痫发生过程，从而为进一步的机制研究提供了一系列靶点。
