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实验性脑出血中长链非编码RNA和信使核糖核酸表达的改变——一项初步研究

Altered Long Noncoding RNA and Messenger RNA Expression in Experimental Intracerebral Hemorrhage - a Preliminary Study.

作者信息

Hanjin Cui, Tao Liu, Pengfei Li, Ali Yang, Huajun Zhou, Jiekun Luo, Yang Wang, Tao Tang

机构信息

Institute of Integrative Medicine, Xiangya Hospital, Central South University, Changsha, China.

Department of Gerontology, Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University, Urumqi, China.

出版信息

Cell Physiol Biochem. 2018;45(3):1284-1301. doi: 10.1159/000487464. Epub 2018 Feb 9.

Abstract

BACKGROUND/AIMS: Functional recovery in the chronic phase is a difficult problem in intracerebral hemorrhage (ICH) treatment. Long noncoding RNAs (lncRNAs) are demonstrated to be involved in central nervous system (CNS) disorders. However, the roles of lncRNAs in post-ICH injury and repair are poorly understood, especially those that may be attributed to long-term neurological deficit. The present study depicted the lncRNA and messenger RNA (mRNA) profile by microarray at late stage after an experimental ICH.

METHODS

LncRNA and mRNA microarray was used to first identify differentially expressed genes. Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to determine bio-functions and signaling pathways, with which differentially expressed genes are most closely related. Quantitative real-time polymerase chain reaction (PCR) was used to validate the results of microarray. Finally, the lncRNA-mRNA co-expression network was constructed to find the interaction of genes.

RESULTS

A total of 625 differentially expressed lncRNAs and 826 expressed mRNAs were identified. Altered genes were enriched in mitochon-drial matrix, G-protein coupled receptor signaling pathway, and olfactory transduction, which may be associated with ICH-induced pathophysiologic changes in the long term. A co-expression network profile based on 5 validated differentially expressed lncRNAs and 205 interacted mRNAs was composed of 210 nodes and 298 connections.

CONCLUSION

Mitochondrial matrix, reduced G-protein coupled receptor activity, and impaired olfactory transduction may be involved in the sequelae following ICH. Further, these dysregulated lncRNAs and mRNAs may be the promising therapeutic targets to overcome obstacles in functional recovery following ICH.

摘要

背景/目的:慢性期功能恢复是脑出血(ICH)治疗中的一个难题。长链非编码RNA(lncRNA)已被证明参与中枢神经系统(CNS)疾病。然而,lncRNA在脑出血后损伤和修复中的作用尚不清楚,尤其是那些可能导致长期神经功能缺损的作用。本研究通过微阵列描绘了实验性脑出血后期的lncRNA和信使RNA(mRNA)图谱。

方法

首先使用lncRNA和mRNA微阵列鉴定差异表达基因。进行基因本体(GO)和京都基因与基因组百科全书(KEGG)通路分析,以确定差异表达基因最密切相关的生物功能和信号通路。使用定量实时聚合酶链反应(PCR)验证微阵列结果。最后,构建lncRNA-mRNA共表达网络以发现基因间的相互作用。

结果

共鉴定出625个差异表达的lncRNA和826个表达的mRNA。改变的基因富集在线粒体基质、G蛋白偶联受体信号通路和嗅觉转导中,这可能与脑出血长期引起的病理生理变化有关。基于5个验证的差异表达lncRNA和205个相互作用的mRNA组成的共表达网络图谱由210个节点和298个连接组成。

结论

线粒体基质、G蛋白偶联受体活性降低和嗅觉转导受损可能参与脑出血后的后遗症。此外,这些失调的lncRNA和mRNA可能是克服脑出血后功能恢复障碍的有前景的治疗靶点。

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