Xiao Yousheng, Chen Hongchang, Liao Jiajia, Zhang Qinxin, He Honghu, Lei Jiang, Huang Jinjun, Ouyang Qiang, Shen Yuefei, Wang Jin
Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Department of Neurology, Minzu Hospital of Guangxi Zhuang Autonomous Region, Nanning, China.
Front Neurosci. 2022 May 13;16:893713. doi: 10.3389/fnins.2022.893713. eCollection 2022.
Parkinson's disease (PD) is a progressive neurodegenerative disease. It has been reported that circular RNAs (circRNAs) play important roles in several neurological diseases. However, the role and regulatory networks of circRNAs in PD are still largely unclear. In this study, we first compared the global expression level of circRNAs from patients with PD and controls using microarray, then the candidate circRNAs were validated in another PD cohort. The possible functions of these candidate circRNAs were analyzed using Gene Ontology (GO) analyses and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, and the regulatory networks of these candidate circRNAs were constructed through circRNA-miRNA-mRNA regulatory networks, protein-protein interaction (PPI) networks, and transcription factor-circRNA networks. The results indicated that hsa_circRNA_101275, hsa_circRNA_103730, and hsa_circRNA_038416 were significantly more highly expressed in patients with PD, while hsa_circRNA_102850 was lower expressed in patients with PD when compared with controls. A circRNA panel combining the four differentially expressed circRNA showed a high diagnostic ability to distinguish patients with PD from controls (AUC = 0.938). Furthermore, GO and KEGG analysis showed these candidate circRNAs were enriched in PI3K-Akt and MAPK signaling pathways. We established circRNA-miRNA-mRNA regulatory networks and identified 10 hub genes (, , , , , , , , , and ) were closely related to PD by using PPI network analysis. Besides, these circRNAs were predicted to be regulated through tyrosine hydroxylase (TH)-relevant transcription factors such as and . In conclusion, our results suggest that the circRNA panel and the established circRNA-miRNA-mRNA regulation networks might provide potential novel biomarkers and therapeutic targets for PD.
帕金森病（PD）是一种进行性神经退行性疾病。据报道，环状RNA（circRNA）在几种神经疾病中发挥重要作用。然而，circRNA在PD中的作用和调控网络仍不清楚。在本研究中，我们首先使用微阵列比较了PD患者和对照组中circRNA的整体表达水平，然后在另一个PD队列中验证了候选circRNA。使用基因本体（GO）分析和京都基因与基因组百科全书（KEGG）分析来分析这些候选circRNA的可能功能，并通过circRNA- miRNA -mRNA调控网络、蛋白质-蛋白质相互作用（PPI）网络和转录因子-circRNA网络构建这些候选circRNA的调控网络。结果表明，hsa_circRNA_101275、hsa_circRNA_103730和hsa_circRNA_038416在PD患者中显著高表达，而与对照组相比，hsa_circRNA_102850在PD患者中低表达。结合这四种差异表达circRNA的circRNA组合显示出区分PD患者和对照组的高诊断能力（AUC = 0.938）。此外，GO和KEGG分析表明这些候选circRNA在PI3K-Akt和MAPK信号通路中富集。我们通过PPI网络分析建立了circRNA-miRNA-mRNA调控网络，并鉴定出10个与PD密切相关的枢纽基因（，，，，，，，，，和）。此外，预测这些circRNA通过酪氨酸羟化酶（TH）相关转录因子如和进行调控。总之，我们的结果表明circRNA组合和建立的circRNA-miRNA-mRNA调控网络可能为PD提供潜在的新型生物标志物和治疗靶点。
