High-Throughput Sequencing and Co-Expression Network Analysis of lncRNAs and mRNAs in Early Brain Injury Following Experimental Subarachnoid Haemorrhage.
High-Throughput Sequencing and Co-Expression Network Analysis of lncRNAs and mRNAs in Early Brain Injury Following Experimental Subarachnoid Haemorrhage.
复制标题
实验性蛛网膜下腔出血后早期脑损伤中 lncRNA 和 mRNA 的高通量测序和共表达网络分析。
DOI：
10.1038/srep46577
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发表时间：
2017-04-18
影响因子：
4.6
通讯作者：
Jiang Y
中科院分区：
文献类型：
--
作者：
Peng J;Wu Y;Tian X;Pang J;Kuai L;Cao F;Qin X;Zhong J;Li X;Li Y;Sun X;Chen L;Jiang Y
蛛网膜下腔出血（SAH）是脑动脉瘤破裂后的一种致死性神经血管疾病，具有较高的发病率和死亡率。长链非编码RNA（longnon-codingRNA，lncRNA）是哺乳动物基因组的一种转录本，在脑内大量表达，与多种神经系统疾病有关。然而，目前对lncRNA在SAH后早期脑损伤（EBI）中的影响知之甚少。本研究采用高通量测序技术分析了小鼠SAH脑组织中lncRNA和mRNA的表达谱。结果表明，SAH组lncRNA和mRNA转录水平与对照组相比有显著性差异。在SAH后24小时，约有617个lncRNA转录本和441个mRNA转录本异常表达。基因本体（GO）富集和京都基因与基因组百科全书（KEGG）分析表明，差异表达的mRNA主要与炎症相关。基于lncRNA/mRNA共表达网络，敲低fantom3_F730004F19降低了BV-2小胶质细胞中CD 14和toll样受体4（TLR 4）的mRNA和蛋白水平，并减轻了炎症。这些结果表明lncRNA fantom3_F730004F19可能与SAH后EBI中小胶质细胞通过TLR信号通路诱导的炎症相关。LncRNA代表了SAH预后、诊断和治疗的潜在治疗靶点。
Subarachnoid haemorrhage (SAH) is a fatal neurovascular disease following cerebral aneurysm rupture with high morbidity and mortality rates. Long non-coding RNAs (lncRNAs) are a type of mammalian genome transcript, are abundantly expressed in the brain and are involved in many nervous system diseases. However, little is currently known regarding the influence of lncRNAs in early brain injury (EBI) after SAH. This study analysed the expression profiles of lncRNAs and mRNAs in SAH brain tissues of mice using high-throughput sequencing. The results showed a remarkable difference in lncRNA and mRNA transcripts between SAH and control brains. Approximately 617 lncRNA transcripts and 441 mRNA transcripts were aberrantly expressed at 24 hours after SAH. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that the differentially expressed mRNAs were mostly involved in inflammation. Based on the lncRNA/mRNA co-expression network, knockdown of fantom3_F730004F19 reduced the mRNA and protein levels of CD14 and toll-like receptor 4 (TLR4) and attenuated inflammation in BV-2 microglia cells. These results indicate that lncRNA fantom3_F730004F19 may be associated with microglia induced inflammation via the TLR signaling pathway in EBI following SAH. LncRNA represent a potential therapeutic target for the prognosis, diagnosis, and treatment of SAH.