A novel microRNA and transcription factor mediated regulatory network in schizophrenia.
A novel microRNA and transcription factor mediated regulatory network in schizophrenia.
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DOI：
10.1186/1752-0509-4-10
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发表时间：
2010-02-15
影响因子：
--
通讯作者：
Zhao Z
中科院分区：
文献类型：
--
作者：
Guo AY;Sun J;Jia P;Zhao Z
精神分裂症是一种复杂的脑部疾病，其分子机制尚未阐明。先前的研究表明，基因表达的变化可能在精神分裂症的病因学中发挥重要作用，而微小RNA（miRNA）和转录因子（TF）是该基因表达的主要调节因子。到目前为止，几个miRNA-TF介导的调控模块已经得到验证。我们假设 miRNA 和 TF 可能对精神分裂症基因发挥组合调控作用，因此探索了精神分裂症中的 miRNA-TF 调控网络。我们在编译的精神分裂症相关 miRNA、TF 和基因中鉴定出了 32 个前馈环 (FFL)。我们的评估表明，这些观察到的 FFL 中精神分裂症基因显着富集。通过融合 FFL 和相互反馈环路，我们构建了一个新型的精神分裂症 miRNA-TF 调控网络。我们的分析显示 EGR3 和 hsa-miR-195 是该调控网络中的核心调控因子。接下来我们提出了一个模型，强调 EGR3 和 miRNA 参与神经系统的信号通路和调节网络。最后，我们提出了位于 miRNA、其靶位点和 TFBS 上的几个单核苷酸多态性 (SNP)，它们可能对精神分裂症基因调控有影响。这项研究为精神分裂症相关基因的调控机制提供了许多见解。它代表了对复杂疾病（如精神分裂症）的 miRNA-TF 调控网络的首次研究。
Schizophrenia is a complex brain disorder with molecular mechanisms that have yet to be elucidated. Previous studies have suggested that changes in gene expression may play an important role in the etiology of schizophrenia, and that microRNAs (miRNAs) and transcription factors (TFs) are primary regulators of this gene expression. So far, several miRNA-TF mediated regulatory modules have been verified. We hypothesized that miRNAs and TFs might play combinatory regulatory roles for schizophrenia genes and, thus, explored miRNA-TF regulatory networks in schizophrenia. We identified 32 feed-forward loops (FFLs) among our compiled schizophrenia-related miRNAs, TFs and genes. Our evaluation revealed that these observed FFLs were significantly enriched in schizophrenia genes. By converging the FFLs and mutual feedback loops, we constructed a novel miRNA-TF regulatory network for schizophrenia. Our analysis revealed EGR3 and hsa-miR-195 were core regulators in this regulatory network. We next proposed a model highlighting EGR3 and miRNAs involved in signaling pathways and regulatory networks in the nervous system. Finally, we suggested several single nucleotide polymorphisms (SNPs) located on miRNAs, their target sites, and TFBSs, which may have an effect in schizophrenia gene regulation. This study provides many insights on the regulatory mechanisms of genes involved in schizophrenia. It represents the first investigation of a miRNA-TF regulatory network for a complex disease, as demonstrated in schizophrenia.
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影响因子：
64.8
作者：
Baek, Daehyun;Villen, Judit;Shin, Chanseok;Camargo, Fernando D.;Gygi, Steven P.;Bartel, David P.
通讯作者：
Bartel, David P.
影响因子：
56.9
作者：
Kim, Jongpil;Inoue, Keiichi;Abeliovich, Asa
通讯作者：
Abeliovich, Asa
DOI：
10.1073/pnas.1432927100
发表时间：
2003-07-22
影响因子：
11.1
作者：
Gerber, DJ;Hall, D;Tonegawa, S
通讯作者：
Tonegawa, S
影响因子：
11.2
作者：
Bracken, Cameron P.;Gregory, Philip A.;Goodall, Gregory J.
通讯作者：
Goodall, Gregory J.
影响因子：
64.5
作者：
Graef, IA;Wang, F;Crabtree, GR
通讯作者：
Crabtree, GR