Department of Neurology, West China Hospital, Sichuan University, Wai Nan Guo Xue Lane 37 #, 610041, Chengdu, Sichuan, China.
BMC Genomics. 2021 Aug 17;22(1):621. doi: 10.1186/s12864-021-07921-7.
Long noncoding RNAs (lncRNAs) play an important role in many neurological diseases. This study aimed to investigate differentially expressed lncRNAs and messenger RNAs (mRNAs) in the susceptibility gaining process of primed DBA/1 mice, a sudden unexpected death in epilepsy (SUDEP) model, to illustrate the potential role of lncRNAs in SUDEP.
The Arraystar mouse lncRNA Microarray V3.0 (Arraystar, Rockville, MD) was applied to identify the aberrantly expressed lncRNAs and mRNAs between primed DBA/1 mice and normal controls. The differences were verified by qRT-PCR. We conducted gene ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and coexpression analyses to explore the possible function of the dysregulated RNAs.
A total of 502 lncRNAs (126 upregulated and 376 downregulated lncRNAs) and 263 mRNAs (141 upregulated and 122 downregulated mRNAs) were dysregulated with P < 0.05 and a fold change over 1.5, among which Adora3 and Gstt4 were possibly related to SUDEP. GO analysis revealed that chaperone cofactor-dependent protein refolding and misfolded protein binding were among the top ten downregulated terms, which pointed to Hspa1a, Hspa2a and their related lncRNAs. KEGG analysis identified 28 upregulated and 10 downregulated pathways. Coexpression analysis showed fifteen dysregulated long intergenic noncoding RNAs (lincRNAs) and three aberrantly expressed antisense lncRNAs, of which AK012034 and NR_040757 are potentially related to SUDEP by regulating LMNB2 and ITPR1, respectively.
LncRNAs and their coexpression mRNAs are dysregulated in the priming process of DBA/1 in the brainstem. Some of these mRNAs and lncRNAs may be related to SUDEP, including Adora3, Lmnb2, Hspa1a, Hspa1b, Itrp1, Gstt4 and their related lncRNAs. Further study on the mechanism of lncRNAs in SUDEP is needed.
长非编码 RNA（lncRNA）在许多神经疾病中发挥重要作用。本研究旨在探讨在引发 DBA/1 小鼠（癫痫猝死症 SUDEP 模型）易感性获得过程中差异表达的 lncRNA 和信使 RNA（mRNA），以阐明 lncRNA 在 SUDEP 中的潜在作用。
采用 Arraystar 小鼠 lncRNA Microarray V3.0（Arraystar，马里兰州罗克维尔）鉴定引发的 DBA/1 小鼠与正常对照之间差异表达的 lncRNA 和 mRNA。通过 qRT-PCR 验证差异。我们进行了基因本体（GO）、京都基因与基因组百科全书（KEGG）通路和共表达分析，以探讨失调 RNA 的可能功能。
共有 502 个 lncRNA（126 个上调和 376 个下调 lncRNA）和 263 个 mRNA（141 个上调和 122 个下调 mRNA）发生了差异表达，P 值均小于 0.05，倍数变化均超过 1.5，其中 Adora3 和 Gstt4 可能与 SUDEP 相关。GO 分析显示，伴侣蛋白辅助因子依赖的蛋白质重折叠和错误折叠蛋白质结合是前 10 个下调的术语之一，涉及 Hspa1a、Hspa2a 及其相关 lncRNA。KEGG 分析鉴定了 28 个上调和 10 个下调的通路。共表达分析显示 15 个差异表达的长非编码基因间非编码 RNA（lncRNA）和 3 个异常表达的反义 lncRNA，其中 AK012034 和 NR_040757 分别通过调节 LMNB2 和 ITPR1 可能与 SUDEP 相关。
在 DBA/1 脑干的引发过程中，lncRNA 及其共表达的 mRNA 发生了失调。其中一些 mRNA 和 lncRNA 可能与 SUDEP 相关，包括 Adora3、Lmnb2、Hspa1a、Hspa1b、Itrp1、Gstt4 及其相关 lncRNA。需要进一步研究 lncRNA 在 SUDEP 中的作用机制。
