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首页> 外文期刊>International Journal of Molecular Sciences >Transcriptomic Profiling of Circular RNA in Different Brain Regions of Parkinson’s Disease in a Mouse Model
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Transcriptomic Profiling of Circular RNA in Different Brain Regions of Parkinson’s Disease in a Mouse Model

机译:在小鼠模型中帕金森病不同脑区圆形RNA的转录组分析

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Parkinson’s disease (PD) is the second most common neurodegenerative disease and although many studies have been done on this disease, the underlying mechanisms are still poorly understood and further studies are warranted. Therefore, this study identified circRNA expression profiles in the cerebral cortex (CC), hippocampus (HP), striatum (ST), and cerebellum (CB) regions of the 1-methyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model using RNA sequencing (RNA-seq), and differentially expressed circRNA were validated using reverse transcription quantitative real-time PCR (qRT-PCR). Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and competing endogenous RNA (ceRNA) network analyses were also performed to explore the potential function of circRNAs. The results show that, compared with the control group, 24, 66, 71, and 121 differentially expressed circRNAs (DE-circRNAs) were found in the CC, HP, ST, and CB, respectively. PDST vs. PDCB, PDST vs. PDHP, and PDCB vs. PDHP groups have 578, 110, and 749 DE-circRNAs, respectively. Then, seven DE-cirRNAs were selected for qRT-PCR verification, where the expressions were consistent with the sequencing analysis. The GO and KEGG pathway analyses revealed that these DE-circRNAs participate in several biological functions and signaling pathways, including glutamic synapse, neuron to neuron synapse, cell morphogenesis involved in neuron differentiation, Parkinson’s disease, axon guidance, cGMP-PKG signaling pathway, and PI3K-Akt signaling pathway. Furthermore, the KEGG analysis of the target genes predicted by DE-circRNAs indicated that the target genes predicted by mmu_circRNA_0003292, mmu_circRNA_0001320, mmu_circRNA_0005976, and mmu_circRNA_0005388 were involved in the PD-related pathway. Overall, this is the first study on the expression profile of circRNAs in the different brain regions of PD mouse model. These results might facilitate our understanding of the potential roles of circRNAs in the pathogenesis of PD. Moreover, the results also indicate that the mmu_circRNA_0003292-miRNA-132-Nr4a2 pathway might be involved in the regulation of the molecular mechanism of Parkinson’s disease.
机译:帕金森病(PD)是第二种最常见的神经退行性疾病,虽然已经对这种疾病进行了许多研究,但潜在的机制仍然明白,并有权进一步研究。因此,该研究确定了1-甲基-1,2,3,6-四氢吡啶(MPTP)的脑皮层(CC),海马(CC),海马(HP),纹状体(ST)和小脑(CB)区域中的脑皮层(CC),海马(ST)和小脑区域)中的CircRNA表达谱诱导使用RNA测序(RNA-SEQ)的PD小鼠模型,并使用逆转录定量实时PCR(QRT-PCR)验证差异表达的CircRNA。还进行了基因本体(GO),基因和基因组(KEGG)途径(KEGG)途径和竞争内源性RNA(CERNA)网络分析,以探讨CIRCRNA的潜在功能。结果表明,与对照组,24,66,71和121个差异表达的Circrnas(De-Circrnas)分别在CC,HP,ST和CB中进行比较。 PDST与PDCB,PDST与PDHP和PDCB与PDHP组分别具有578,110和749个de-circrnas。然后,选择七个de-ciRRNA用于QRT-PCR验证,其中表达式与测序分析一致。 Go和Kegg途径分析显示,这些De-Circrnas参与了几种生物功能和信号通路,包括谷氨酸突触,神经元对神经元突触,细胞形态发生,参与神经元分化,帕金森病,轴突引导,CGMP-PKG信号通路,以及PI3K-AKT信号通路。此外,DE-CIRCRNA预测的靶基因的KEGG分析表明由MMU_CIRCRNA_0003292,MMU_CIRCRNA_0001320,MMU_CIRCRNA_0005976和MMU_CIRCRNA_0005388预测的靶基因参与了PD相关途径。总体而言,这是PD小鼠模型不同脑区域中Circrnas表达谱的第一研究。这些结果可能促进了我们对Circrnas在PD发病机制中的潜在作用的理解。此外,结果还表明MMU_CIRCRNA_0003292-MIRNA-132-NR4A2途径可能参与帕金森病的分子机制的调节。

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