中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2019, Vol. 14 ›› Issue (4): 632-641.doi: 10.4103/1673-5374.247467

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

人类创伤性脑损伤组织长非编码RNA和mRNA的表达特征

  

  • 出版日期:2019-04-15 发布日期:2019-04-15
  • 基金资助:

    国家自然科学基金资助(81571939，81601719，81772134)；湖南省重点研究开发项目(2018SK2091)；中国卫生部长伍杰-平医学基金会(320.6750.14118)；中南大学教师研究基金(2014JSJJ026)

Expression signatures of long non-coding RNA and mRNA in human traumatic brain injury

Li-Xiang Yang 1 , Li-Kun Yang 1 , Jie Zhu 1 , Jun-Hui Chen 1 , Yu-Hai Wang 1 , Kun Xiong 2   

  1. 1 Department of Neurosurgery, 101 st Hospital of People’s Liberation Army, Wuxi, Jiangsu Province, China
    2 Department of Anatomy and Neurobiology, School of Basic Medical Sciences, Central South University, Changsha, Hunan Province, China
  • Online:2019-04-15 Published:2019-04-15
  • Contact: Kun Xiong, MD, PhD, xiongkun2001@163.com; Yu-Hai Wang, MD, PhD, wangyuhai101@126.com.
  • Supported by:

    This study was supported by the National Natural Science Foundation of China, No. 81571939 (to KX), 81601719 (to JZ) and 81772134 (to KX); the Key Research and Development Program of Hunan Province of China, No. 2018SK2091 (to KX); the Wu Jie-Ping Medical Foundation of the Minister of Health of China, No. 320.6750.14118 (to KX); and the Teacher Research Foundation of Central South University of China, No. 2014JSJJ026 (to KX).

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摘要：

长链非编码RNA(lncRNA)在颅脑疾病中可发挥重要作用，但是在人类创伤性脑损伤(TBI)组织中的表达谱仍不清楚。为此，研究纳入解放军第101医院3例（36岁男性1例，52岁及49岁女性各1例）被诊断为创伤性脑损伤并接受脑挫伤清除手术患者的损伤脑组织，将此3例患者脑挫伤部位周围组织设为对照，以此观察人类创伤性脑损伤组织长非编码RNA和mRNA的表达特征。(1) Volcano Plot filtering检测发现，两组额颞部组织具有差异表达的99个lncRNAs和63个mRNAs(P < 0.05，fold change > 1.2)；(2)基因芯片检测显示，两组发现43个lncRNAs表达上调，56个lncRNAs表达下调，59个mRNA表达上调，4个mRNA表达下调；(3) GO及KEGG分析发现，27种信号通路与靶基因有关，特别是Legionellosis和Influenza A信号通路；(4)随后实验构建了lncRNA-基因网络，并发现12对lncRNA-mRNA的相关系数绝对值大于0.99；(5)最后，通过RT-qPCR法验证了在两组中所选上调最显著的5个mRNA的表达情况，这也与基因芯片检测结果一致；(6)上述数据说明，在人创伤性脑损伤组织和周围组织中，mRNA及LncRNA的表达谱均有显著差异，这为人类TBI中涉及LncRNAs的治疗提供了新的视野。本研究对象均签署知情同意书，并已在中国临床试验注册中心注册(注册号：ChiCTR-TCC-13004002)，试验方案版本号1.0。

orcid: 0000-0002-3103-6028(Kun Xiong)
          0000-0002-8076-6756(Yu-Hai Wang)

关键词: 人创伤性脑损伤, 长非编码RNA, 信使RNA, GO分析, RT-qPCR, 生物标志物, 微阵列分析, 生物过程, 医学信息学, 神经再生

Abstract:

Long non-coding RNAs (lncRNAs) play a key role in craniocerebral disease, although their expression profiles in human traumatic brain injury are still unclear. In this regard, in this study, we examined brain injury tissue from three patients of the 101st Hospital of the Peo¬ple’s Liberation Army, China (specifically, a 36-year-old male, a 52-year-old female, and a 49-year-old female), who were diagnosed with traumatic brain injury and underwent brain contusion removal surgery. Tissue surrounding the brain contusion in the three patients was used as control tissue to observe expression characteristics of lncRNAs and mRNAs in human traumatic brain injury tissue. Volcano plot filtering identified 99 lncRNAs and 63 mRNAs differentially expressed in frontotemporal tissue of the two groups (P < 0.05, fold change > 1.2). Microarray analysis showed that 43 lncRNAs were up-regulated and 56 lncRNAs were down-regulated. Meanwhile, 59 mRNAs were up-regulated and 4 mRNAs were down-regulated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed 27 signaling pathways associated with target genes and, in particular, legionellosis and influenza A signaling pathways. Subsequently, a lncRNA-gene network was generated, which showed an absolute correlation coefficient value > 0.99 for 12 lncRNA-mR¬NA pairs. Finally, quantitative real-time polymerase chain reaction confirmed different expression of the five most up-regulated mRNAs within the two groups, which was consistent with the microarray results. In summary, our results show that expression profiles of mRNAs and lncRNAs are significantly different between human traumatic brain injury tissue and surrounding tissue, providing novel insight re¬garding lncRNAs’ involvement in human traumatic brain injury. All participants provided informed consent. This research was registered in the Chinese Clinical Trial Registry (registration number: ChiCTR-TCC-13004002) and the protocol version number is 1.0.

Key words: nerve regeneration, human traumatic brain injuries, long noncoding RNA, messenger RNA, GO analysis, real-time quantitative polymerase chain reaction, biomarkers, microarray analysis, biological processes, medical informatics, neural regeneration