解剖学报 ›› 2023, Vol. 54 ›› Issue (4): 405-413.doi: 10.16098/j.issn.0529-1356.2023.04.005

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基于全转录组技术研究慢性应激抑郁模型中微小RNA、长链非编码RNA及环状RNA的表达谱及调控网络

孟盼1 张熙2 杨蕙3 刘检3 方锐4 王枭冶2*  葛金文1,4*  刘彤彤5 赵洪庆5 王宇红5   

  1. 1.湖南中医药大学中西医结合学院,长沙 410208;  2.湖南省脑科医院科研部,长沙 410007;3.湖南中医药大学第一附属医院医学实验中心,长沙 410007;   4.湖南省中医药研究院,长沙 410006; 5.湖南中医药大学科技创新中心,长沙 410208
  • 收稿日期:2022-01-13 修回日期:2022-04-15 出版日期:2023-08-06 发布日期:2023-08-06
  • 通讯作者: 王枭冶;葛金文 E-mail:15236914662@163.com
  • 基金资助:
    湖南省自然科学基金优秀青年项目;湖南省科技创新人才计划优秀博士后创新人才项目;长沙市杰出创新青年培养计划

Expression profiles and regulatory network of microRNA, long non-coding RNA and circular RNA in rat chronic stress depression model based on whole transcriptome technology

MENG  Pan ZHANG Xi YANG  Hui3  LIU  Jian3  FANG  Rui4  WANG  Xiao-ye2*  GE  Jin-wen1,4* LIU  Tong-tong5 ZHAO  Hong-qing5  WANG  Yu-hong5#br#   

  1. 1. School of Integrated Chinese and Western Medicine, Hu’nan University of Chinese Medicine, Changsha 410208, China; 2.Department of Scientific Research, Brain Hospital of Hu’nan Province, Changsha 410007, China;   3.Center for Medical Research and Innovation, the First Hospital of Hunan University of Chinese Medicine, Changsha 410007, China;  4.Hu’nan Academy of Traditional Chinese Medicine, Changsha 410006, China;  5. Science and Technology Innovation Center, Hu’nan University of Chinese Medicine, Changsha 410208, China

  • Received:2022-01-13 Revised:2022-04-15 Online:2023-08-06 Published:2023-08-06
  • Contact: WANG Xiao-ye;GE Jin-wen E-mail:15236914662@163.com

摘要:

目的  筛选慢性应激抑郁模型大鼠海马组织中微小RNA(miRNA)、长链非编码RNA(lncRNA)、环状RNA(circRNA)的表达谱及其竞争性内源RNA(ceRNA)调控网络,探讨抑郁症潜在的病理生理机制。   方法  12只SD 大鼠分为空白组和模型组,采用慢性温和不可预测性应激(CUMS)构建抑郁症大鼠模型,取大鼠海马组织进行全转录组分析,并用生物信息学方法找出可能存在的 lncRNA-miRNA-mRNA、circRNA-miRNA-mRNA调控网络。   结果  根据|差异倍数(fold change)|≥1.5和P≤0.05共鉴定出29个差异miRNAs(上调21个,下调8个),686个差异lncRNAs(上调163个,下调523个),8个差异circRNAs(上调3个,下调5个)。基因本体论(GO)和京都基因和基因组百科全书(KEGG)通路分析显示,miRNAs的靶基因主要富集于细胞膜内的高尔基体和钙离子结合过程;LncRNAs靶基因的功能涉及核酸结合的调节、细胞因子和蛋白质泛素化等;CircRNAs的宿主基因主要集中在细胞刺激反应、代谢进程、催化活性等过程中。LncRNAs和circRNAs相互竞争的ceRNA网络显示,非编码RNA(ncRNA)与突触可塑性相关的mRNA之间存在复杂相互作用,如与轴突导向相关的Wnt-ta蛋白(WNT5a)和Ⅷ型胶原α1(COL8α1),以及神经发育相关的层黏连蛋白A2(LAMA2)。   结论  LncRNA和circRNA的ceRNA网络显示,ncRNA和mRNA之间的复杂相互作用与抑郁症的神经可塑性受损有关。

关键词: 微小RNA, 长链非编码RNA, 环状RNA, 抑郁症, 神经可塑性, 全转录组技术, 大鼠

Abstract:

Objective  To explore the potential pathophysiological mechanism of depression by screening the expression profiles and competing endogenous RNA (ceRNA) regulatory network microRNA(miRNA), long non\|coding RNA(lncRNA) and circular RNA(circRNA) in the hippocampus of chronic stress depression rat model.    Methods  Twelve SD rats were divided into blank group and model group. Chronic mild unpredictability stress (CUMS) was used to construct the rat model of depression. The whole transcriptome analysis was performed on the hippocampus of the rats, and the possible regulatory networks among lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA were explored by bioinformatics method.    Results  According to the |fold change|≥1.5 and  P≤0.05, 29 differentially expressed miRNAs (21 up-regulated and 8 down-regulated), 686 differentially expressed lncRNAs (163 up-regulated and 523 down-regulated) and 8 differentially expressed circRNAs (3 up-regulated and 5 down-regulated) were identified. Gene Ontology(GO) and Kytot Encyclopedia of Genes and Genomes(KEGG) pathway analysis showed that the target genes of miRNAs were mainly enriched in the Golgi apparatus and calcium ion binding process in the cell membrane, the functions of lncRNAs target genes involved nucleic acid binding regulation, cytokine and protein ubiquitination, etc, and the functions of host genes of circRNAs were associated with cellular stimulation response, metabolic process, catalytic activity and other processes. The ceRNA network of lncRNAs and circRNAs showed complex interactions between non-coding RNA (ncRNA) and mRNA related to synaptic plasticity, such as protein Wnt-sa(WNT5a) and collagentype Ⅲ alpha1(COL8a1) related to axon orientation and laminin A2(LAMA2) related to neurodevelopment.     Conclusion  The ceRNA network of lncRNA and circRNA shows that the complex interaction betweens ncRNA and mRNA is highly associated with the neuroplasticity, which support the neuroplasticity hypothesis of depression. 

Key words: MicroRNA, Long non-coding RNA, Circular RNA, Depression, Neuroplasticity, Whole transcriptome technology, Rat

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