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。
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 andP≤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 collagentypeⅢalpha1(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.
作者
孟盼
张熙
杨蕙
刘检
方锐
王枭冶
葛金文
刘彤彤
赵洪庆
王宇红
MENG Pan;ZHANG Xi;YANG Hui;LIU Jian;FANG Rui;WANG Xiao-ye;GE Jin-wen;LIU Tong-tong;ZHAO Hong-qing;WANG Yu-hong(School of Integrated Chinese and Western Medicine,Hu’nan University of Chinese Medicine,Changsha 410208,China;Department of Scientific Research,Brain Hospital of Hu’nan Province,Changsha 410007,China;Center for Medical Research and Innovation,the First Hospital of Hunan University of Chinese Medicine,Changsha 410007,China;Hu’nan Academy of Traditional Chinese Medicine,Changsha 410006,China;Science and Technology Innovation Center,Hu’nan University of Chinese Medicine,Changsha 410208,China)
出处
《解剖学报》
CAS
CSCD
北大核心
2023年第4期405-413,共9页
Acta Anatomica Sinica
基金
湖南省自然科学基金优秀青年基金(2020JJ3027)
湖南省科技创新人才计划优秀博士后创新人才项目(2020RC2060)
长沙市杰出创新青年计划项目(kq2009018)。
