Integrative analysis of long noncoding RNAs dysregulation and synapse-associated ceRNA regulatory axes in autism.
Integrative analysis of long noncoding RNAs dysregulation and synapse-associated ceRNA regulatory axes in autism.
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DOI：
10.1038/s41398-023-02662-5
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发表时间：
2023-12-06
影响因子：
6.8
通讯作者：
Wang, Lifang
中科院分区：
文献类型：
--
作者：
Jiang, Miaomiao;Wang, Ziqi;Lu, Tianlan;Li, Xianjing;Yang, Kang;Zhao, Liyang;Zhang, Dai;Li, Jun;Wang, Lifang
自闭症谱系障碍（ASD）是一种复杂的神经发育障碍，长链非编码RNA（lncRNA）在ASD中的功能尚不清楚。在本研究中，基因网络被用于探索ASD疾病机制，整合多种数据类型（例如，RNA表达，全外显子组测序信号，加权基因共表达网络分析和蛋白质-蛋白质相互作用）和数据集（5个人类死后数据集）。共发现388个lncRNA和5个共表达模块在ASD中发生改变。下调的共表达M4模块与ASD显著相关，富含自闭症易感基因和突触信号。整合来自M4模块的lncRNA和来自文献的microRNA（miRNA）失调数据鉴定了竞争性内源RNA（ceRNA）网络。我们通过miRTarBase、miRDB和TargetScan数据库鉴定了与miRNA相互作用的下调mRNA。我们的分析表明，MIR 600 HG在多个脑组织数据集中下调，并与ceRNA网络中的9个自闭症易感miRNAs密切相关。通过定量逆转录聚合酶链反应分析，MIR 600 HG和靶mRNA（EPHA 4、MOAP 1、MAP 3 K9、STXBP 1、PRKCE和SCAMP 5）在外周血中下调（假发现率<0.05）。随后，我们评估了lncRNA失调在mRNA水平改变中的作用。实验验证表明，MIR 600 HG敲低后，一些突触相关的mRNA表达下调。BrainSpan项目发现，在人类不同脑区和不同发育阶段，MIR 600 HG（primate-specific lncRNA）和突触相关mRNA的表达模式相似。支持向量机和随机森林机器学习算法的组合在ceRNA网络中检索ASD的标记基因，诊断诺模图的曲线下面积为0.851。总之，MIR 600 HG，一种与ASD相关的新型特异性lncRNA，调节异常负责ASD相关的miRNA-mRNA轴，从而潜在地调节突触发生。
Autism spectrum disorder (ASD) is a complex disorder of neurodevelopment, the function of long noncoding RNA (lncRNA) in ASD remains essentially unknown. In the present study, gene networks were used to explore the ASD disease mechanisms integrating multiple data types (for example, RNA expression, whole-exome sequencing signals, weighted gene co-expression network analysis, and protein-protein interaction) and datasets (five human postmortem datasets). A total of 388 lncRNAs and five co-expression modules were found to be altered in ASD. The downregulated co-expression M4 module was significantly correlated with ASD, enriched with autism susceptibility genes and synaptic signaling. Integrating lncRNAs from the M4 module and microRNA (miRNA) dysregulation data from the literature identified competing endogenous RNA (ceRNA) network. We identified the downregulated mRNAs that interact with miRNAs by the miRTarBase, miRDB, and TargetScan databases. Our analysis reveals that MIR600HG was downregulated in multiple brain tissue datasets and was closely associated with 9 autism-susceptible miRNAs in the ceRNA network. MIR600HG and target mRNAs (EPHA4, MOAP1, MAP3K9, STXBP1, PRKCE, and SCAMP5) were downregulated in the peripheral blood by quantitative reverse transcription polymerase chain reaction analysis (false discovery rate <0.05). Subsequently, we assessed the role of lncRNA dysregulation in altered mRNA levels. Experimental verification showed that some synapse-associated mRNAs were downregulated after the MIR600HG knockdown. BrainSpan project showed that the expression patterns of MIR600HG (primate-specific lncRNA) and synapse-associated mRNA were similar in different human brain regions and at different stages of development. A combination of support vector machine and random forest machine learning algorithms retrieved the marker gene for ASD in the ceRNA network, and the area under the curve of the diagnostic nomogram was 0.851. In conclusion, dysregulation of MIR600HG, a novel specific lncRNA associated with ASD, is responsible for the ASD-associated miRNA-mRNA axes, thereby potentially regulating synaptogenesis.
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WGCNA：用于加权相关网络分析的 R 包。
影响因子：
3
作者：
Langfelder P;Horvath S
通讯作者：
Horvath S
长链非编码 RNA 在癌症中的作用、功能和机制。
DOI：
10.1016/j.gpb.2015.09.006
发表时间：
2016-02
期刊：
Genomics, proteomics & bioinformatics
影响因子：
--
作者：
Fang Y;Fullwood MJ
通讯作者：
Fullwood MJ
DOI：
10.1016/s1474-4422(15)00044-7
发表时间：
2015-11
期刊：
The Lancet. Neurology
影响因子：
--
作者：
Geschwind DH;State MW
通讯作者：
State MW
影响因子：
64.8
作者：
Iossifov, Ivan;O'Roak, Brian J.;Sanders, Stephan J.;Ronemus, Michael;Krumm, Niklas;Levy, Dan;Stessman, Holly A.;Witherspoon, Kali T.;Vives, Laura;Patterson, Karynne E.;Smith, Joshua D.;Paeper, Bryan;Nickerson, Deborah A.;Dea, Jeanselle;Dong, Shan;Gonzalez, Luis E.;Mandell, Jeffrey D.;Mane, Shrikant M.;Murtha, Michael T.;Sullivan, Catherine A.;Walker, Michael F.;Waqar, Zainulabedin;Wei, Liping;Willsey, A. Jeremy;Yamrom, Boris;Lee, Yoon-ha;Grabowska, Ewa;Dalkic, Ertugrul;Wang, Zihua;Marks, Steven;Andrews, Peter;Leotta, Anthony;Kendall, Jude;Hakker, Inessa;Rosenbaum, Julie;Ma, Beicong;Rodgers, Linda;Troge, Jennifer;Narzisi, Giuseppe;Yoon, Seungtai;Schatz, Michael C.;Ye, Kenny;McCombie, W. Richard;Shendure, Jay;Eichler, Evan E.;State, Matthew W.;Wigler, Michael
通讯作者：
Wigler, Michael
影响因子：
5.3
作者：
Casey JP;Magalhaes T;Conroy JM;Regan R;Shah N;Anney R;Shields DC;Abrahams BS;Almeida J;Bacchelli E;Bailey AJ;Baird G;Battaglia A;Berney T;Bolshakova N;Bolton PF;Bourgeron T;Brennan S;Cali P;Correia C;Corsello C;Coutanche M;Dawson G;de Jonge M;Delorme R;Duketis E;Duque F;Estes A;Farrar P;Fernandez BA;Folstein SE;Foley S;Fombonne E;Freitag CM;Gilbert J;Gillberg C;Glessner JT;Green J;Guter SJ;Hakonarson H;Holt R;Hughes G;Hus V;Igliozzi R;Kim C;Klauck SM;Kolevzon A;Lamb JA;Leboyer M;Le Couteur A;Leventhal BL;Lord C;Lund SC;Maestrini E;Mantoulan C;Marshall CR;McConachie H;McDougle CJ;McGrath J;McMahon WM;Merikangas A;Miller J;Minopoli F;Mirza GK;Munson J;Nelson SF;Nygren G;Oliveira G;Pagnamenta AT;Papanikolaou K;Parr JR;Parrini B;Pickles A;Pinto D;Piven J;Posey DJ;Poustka A;Poustka F;Ragoussis J;Roge B;Rutter ML;Sequeira AF;Soorya L;Sousa I;Sykes N;Stoppioni V;Tancredi R;Tauber M;Thompson AP;Thomson S;Tsiantis J;Van Engeland H;Vincent JB;Volkmar F;Vorstman JA;Wallace S;Wang K;Wassink TH;White K;Wing K;Wittemeyer K;Yaspan BL;Zwaigenbaum L;Betancur C;Buxbaum JD;Cantor RM;Cook EH;Coon H;Cuccaro ML;Geschwind DH;Haines JL;Hallmayer J;Monaco AP;Nurnberger JI Jr;Pericak-Vance MA;Schellenberg GD;Scherer SW;Sutcliffe JS;Szatmari P;Vieland VJ;Wijsman EM;Green A;Gill M;Gallagher L;Vicente A;Ennis S
通讯作者：
Ennis S