Expression and functional analysis of lncRNAs in the hippocampus of immature rats with status epilepticus
Expression and functional analysis of lncRNAs in the hippocampus of immature rats with status epilepticus
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幼年癫痫持续状态大鼠海马lncRNA的表达及功能分析
DOI：
10.1111/jcmm.14676
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发表时间：
2019-11-18
影响因子：
5.3
通讯作者：
Mu, Dezhi
中科院分区：
文献类型：
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作者：
Gan, Jing;Huang, Lingyi;Mu, Dezhi
长链非编码RNA（lncRNA）在不同水平上参与基因表达的调控。然而，迄今为止，lncRNA在癫痫持续状态（SE）中的表达谱尚不清楚。在我们的研究中，lncRNA的表达谱进行了研究，通过高通量测序的基础上锂/匹罗卡品诱导的SE模型在未成年大鼠。此外，加权相关网络分析（WGCNA），基因本体（GO）分析和京都基因和基因组百科全书（KEGG）分析，以构建共表达网络和确定的枢纽lncRNA在SE中的功能。在体外模型中研究了中枢lncRNA（NONRATT010788.2）在SE中的功能作用。我们的研究结果表明，7082 lncRNA（3522上调和3560下调），参与细胞增殖，炎症反应，血管生成和自噬，在未成年大鼠与SE海马失调。此外，WGCNA在绿松石模块中鉴定了667个上调的hub lncRNA，这些lncRNA通过调节HIF-1，p53和趋化因子信号通路以及通过炎症介质调节TRP通道参与细胞凋亡，炎症反应和血管生成。在体外，敲除已鉴定的中枢lncRNA（NONRATT010788.2）抑制神经元凋亡。总之，我们的研究是第一个证明lncRNA的表达谱和潜在的功能，在未成年大鼠的海马SE。中枢lncRNA可能通过lncRNA-miRNA-mRNA网络参与SE的发病。
Long non-coding RNAs (lncRNAs) have been implicated in the regulation of gene expression at various levels. However, to date, the expression profile of lncRNAs in status epilepticus (SE) was unclear. In our study, the expression profile of lncRNAs was investigated by high-throughput sequencing based on a lithium/pilocarpine-induced SE model in immature rats. Furthermore, weighted correlation network analysis (WGCNA), gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to construct co-expression networks and establish functions of the identified hub lncRNAs in SE. The functional role of a hub lncRNA (NONRATT010788.2) in SE was investigated in an in vitro model. Our results indicated that 7082 lncRNAs (3522 up-regulated and 3560 down-regulated), which are involved in cell proliferation, inflammatory responses, angiogenesis and autophagy, were dysregulated in the hippocampus of immature rats with SE. Additionally, WGCNA identified 667 up-regulated hub lncRNAs in turquoise module that were involved in apoptosis, inflammatory responses and angiogenesis via regulation of HIF-1, p53 and chemokine signalling pathways and via inflammatory mediator regulation of TRP channels. Knockdown of an identified hub lncRNA (NONRATT010788.2) inhibited neuronal apoptosis in vitro. Taken together, our study is the first to demonstrate the expression profile and potential function of lncRNAs in the hippocampus of immature rats with SE. The defined hub lncRNAs may participate in the pathogenesis of SE via lncRNA-miRNA-mRNA network.