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人创伤性脑损伤中长链非编码RNA和信使RNA的表达谱

Expression Profiles of Long Non-coding RNA and Messenger RNA in Human Traumatic Brain Injury.

作者信息

Ren Dabin, Chen Wei, Cao Ke, Wang Zhihan, Zheng Ping

机构信息

Department of Neurosurgery, Pudong New Area People's Hospital, Shanghai 200120, China.

Department of Neurosurgery, Shanghai East Hospital, Shanghai 200120, China.

出版信息

Mol Ther Nucleic Acids. 2020 Aug 19;22:99-113. doi: 10.1016/j.omtn.2020.08.012.

Abstract

Long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) play an important role in central nervous diseases; however, the exact expression and co-expressed profiles in human traumatic brain injury (TBI) are still unknown. Therefore, we investigated whole blood in 12 patients with TBI and 4 healthy controls to observe expression characteristics with different severity. We identified 3,035 lncRNAs and 1,204 mRNAs differentially expressed in the severe TBI group, 2,362 lncRNAs and 656 mRNAs in the moderate group, and 433 lncRNAs and 100 mRNAs in the mild group. Enrichment analyses showed 30 signaling pathways such as inflammatory and immune response pathways. Subsequently, a lncRNA-gene co-expression network was generated for 717 lncRNA-mRNA pairs and most of them with a positive correlation. Based on GSEA analysis, we found that TBI caused severe immune abnormality reflected on Th1, Th2, and Th17 cell differentiation deficiency. Finally, the expression of one upregulated and one downregulated lncRNA was validated in all three TBI groups, which was consistent with the microarray results. In summary, our results show that expression profiles of lncRNAs and mRNAs are significantly different in bloods from different severity TBI especially in immune response, providing novel insight for lncRNAs in human TBI.

摘要

长链非编码RNA(lncRNAs)和信使RNA(mRNAs)在中枢神经疾病中发挥着重要作用;然而,其在人类创伤性脑损伤(TBI)中的具体表达及共表达谱仍不清楚。因此,我们对12例TBI患者和4例健康对照者的全血进行了研究,以观察不同严重程度下的表达特征。我们发现在重度TBI组中有3035个lncRNAs和1204个mRNAs差异表达,中度组中有2362个lncRNAs和656个mRNAs,轻度组中有433个lncRNAs和100个mRNAs。富集分析显示了30条信号通路,如炎症和免疫反应通路。随后,构建了一个包含717对lncRNA - mRNA的lncRNA - 基因共表达网络,其中大多数呈正相关。基于基因集富集分析(GSEA),我们发现TBI导致严重的免疫异常,表现为Th1、Th2和Th17细胞分化缺陷。最后,在所有三个TBI组中验证了一个上调和一个下调lncRNA的表达,这与微阵列结果一致。总之,我们的结果表明,lncRNAs和mRNAs的表达谱在不同严重程度TBI患者的血液中存在显著差异,尤其是在免疫反应方面,这为lncRNAs在人类TBI中的研究提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c31a/7493132/26f16527645a/fx1.jpg

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