Integrative Analysis Extracts a Core ceRNA Network of the Fetal Hippocampus With Down Syndrome.
Integrative Analysis Extracts a Core ceRNA Network of the Fetal Hippocampus With Down Syndrome.
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DOI：
10.3389/fgene.2020.565955
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发表时间：
2020
影响因子：
3.7
通讯作者：
Liao S
中科院分区：
文献类型：
--
作者：
Wang S;Tang X;Qin L;Shi W;Bian S;Wang Z;Wang Q;Wang X;Gu J;Hao B;Ding K;Liao S
越来越多的证据表明，环状RNA（circRNA）--miRNA-mRNA ceRNA调控网络--可能在神经系统疾病如阿尔茨海默病（AD）中发挥重要作用。有趣的是，在几乎所有> 35岁的唐氏综合征（DS）病例中都发现了与AD非常相似的神经病理学变化。然而，很少有研究报道DS病例中的circRNA转录谱，这是由21三体染色体畸变引起的。在这里，我们通过使用微阵列来表征DS患者（n = 8）和对照组（n = 6）的胎儿海马中circRNA的表达谱。我们之前研究中DS的miRNA、mRNA表达谱和描述正常胎儿海马发育（GEO）的scRNA-seq数据也被整合到分析中。通过加权相关网络分析（WGCNA）计算circRNA/基因与性状/细胞类型之间的相似性。米兰达和miRWalk 2用于预测ceRNA网络相互作用。我们总共鉴定了7，078个显著差异表达（DE）的circRNA，分别包括2，637个上调和4，441个下调的基因。WGCNA在scRNA-seq数据中获得了15个hub circRNA和6个具有细胞类型特异性表达模式的模块。最后，构建了由14个hub circRNA、17个DE miRNA靶标和245个DE mRNA靶标组成的核心ceRNA网络，并具有细胞类型特异性表达模式注释。DS或神经变性中的已知功能分子（例如，miR-138、OLIG 1和TPM 2）也包括在该网络中。我们的发现是第一个描绘DS中circRNA的景观，也是第一个有效整合ceRNA调控与scRNA-seq数据的发现。这些数据可能为进一步研究DS神经病变的分子机制或治疗靶点提供了宝贵的资源。
Accumulating evidence suggests that circular RNAs (circRNAs)—miRNA–mRNA ceRNA regulatory network—may play an important role in neurological disorders, such as Alzheimer’s disease (AD). Interestingly, neuropathological changes that closely resemble AD have been found in nearly all Down syndrome (DS) cases > 35 years. However, few studies have reported circRNA transcriptional profiling in DS cases, which is caused by a chromosomal aberration of trisomy 21. Here, we characterized the expression profiles of circRNAs in the fetal hippocampus of DS patients (n = 8) and controls (n = 6) by using microarray. MiRNA, mRNA expression profiling of DS from our previous study and scRNA-seq data describing normal fetal hippocampus development (GEO) were also integrated into the analysis. The similarity between circRNAs/genes with traits/cell-types was calculated by weighted correlation network analysis (WGCNA). miRanda and miRWalk2 were used to predict ceRNA network interactions. We identified a total of 7,078 significantly differentially expressed (DE) circRNAs, including 2,637 upregulated and 4,441 downregulated genes, respectively. WGCNA obtained 15 hub circRNAs and 6 modules with cell type–specific expression patterns among scRNA-seq data. Finally, a core ceRNA network was constructed by 14 hub circRNAs, 17 DE miRNA targets and 245 DE mRNA targets with a cell type–specific expression pattern annotation. Known functional molecules in DS or neurodegeneration (e.g., miR-138, OLIG1, and TPM2) were also included in this network. Our findings are the first to delineate the landscape of circRNAs in DS and the first to effectively integrate ceRNA regulation with scRNA-seq data. These data may provide a valuable resource for further research on the molecular mechanisms or therapeutic targets underlying DS neuropathy.
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