高岭土诱导性脑积水差异表达长非编码 RNA 和信使 RNA 谱的综合分析。

Comprehensive analysis of differentially expressed profiles of long non-coding RNAs and messenger RNAs in kaolin-induced hydrocephalus.

机构信息

Department of Neurology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China; Clinical Research Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.

出版信息

Gene. 2019 May 20;697:184-193. doi: 10.1016/j.gene.2019.02.041. Epub 2019 Feb 21.

DOI:10.1016/j.gene.2019.02.041

PMID:30797995

Abstract

BACKGROUNDS

The pathophysiology of hydrocephalus induced brain damage remains unclear. Long non-coding RNAs (lncRNAs) have been demonstrated to be implicated in many central nervous system diseases. However, the roles of lncRNAs in hydrocephalus injury are poorly understood.

METHODS

The present study depicted the expression profiles of lncRNAs and messenger RNAs (mRNAs) in C57BL/6 mice with kaolin-induced hydrocephalus and saline controls using high-throughput RNA sequencing. Afterward, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to identify potential targets that correlated with hydrocephalus. In addition, co-expression networks and cis- and trans-regulation were predicted using bioinformatics methods. Finally, representative lncRNAs and mRNAs were further validation using quantitative real-time polymerase chain reaction.

RESULTS

A total of 1575 lncRNAs and 1168 mRNAs were differentially expressed (DE) in hydrocephalus. GO and KEGG analyses indicated several immune and inflammatory response-associated pathways may be important in the hydrocephalus. Besides, functional enrichment analysis based on co-expression network showed several similar pathways, such as chemokine signaling pathway, phagosome, MAPK signaling pathway and complement and coagulation cascade. Cis-regulation prediction revealed 5 novel lncRNAs might regulate their nearby coding genes, and trans-regulation revealed several lncRNAs participate in pathways regulated by transcription factors, including BPTF, FOXM1, NR5A2, P2RX5, and NR6A1.

CONCLUSIONS

In conclusion, our results provide candidate genes involved in hydrocephalus and suggest a new perspective on the modulation of lncRNAs in hydrocephalus.

摘要

背景

脑积水引起的脑损伤的病理生理学仍不清楚。长链非编码 RNA（lncRNA）已被证明与许多中枢神经系统疾病有关。然而，lncRNA 在脑积水损伤中的作用知之甚少。

方法

本研究使用高通量 RNA 测序描绘了高岭土诱导的脑积水 C57BL/6 小鼠和盐水对照中 lncRNA 和信使 RNA（mRNA）的表达谱。之后，进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路分析，以确定与脑积水相关的潜在靶点。此外，使用生物信息学方法预测共表达网络和顺式及反式调控。最后，使用定量实时聚合酶链反应进一步验证代表性的 lncRNA 和 mRNA。

结果

脑积水组共有 1575 个 lncRNA 和 1168 个 mRNA 差异表达。GO 和 KEGG 分析表明，几种免疫和炎症反应相关通路可能在脑积水中很重要。此外，基于共表达网络的功能富集分析显示了几个相似的通路，如趋化因子信号通路、吞噬体、MAPK 信号通路和补体及凝血级联。顺式调控预测显示 5 个新的 lncRNA 可能调节其附近的编码基因，反式调控显示几个 lncRNA 参与转录因子调节的通路，包括 BPTF、FOXM1、NR5A2、P2RX5 和 NR6A1。