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基于转录组数据探索帕金森病和克罗恩病的共同基因特征及分子机制

Exploration of the Common Gene Characteristics and Molecular Mechanism of Parkinson's Disease and Crohn's Disease from Transcriptome Data.

作者信息

Zheng Haoran, Qian Xiaohang, Tian Wotu, Cao Li

机构信息

School of Medicine, Anhui University of Science and Technology, Huainan 232001, China.

Department of Neurology Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.

出版信息

Brain Sci. 2022 Jun 13;12(6):774. doi: 10.3390/brainsci12060774.

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disorder, and the mechanism of its occurrence is still not fully elucidated. Accumulating evidence has suggested that the gut acts as a potential origin of PD pathogenesis. Recent studies have identified that inflammatory bowel disease acts as a risk factor for Parkinson's disease, although the underlying mechanisms remain elusive. The aim of this study was to further explore the molecular mechanism between PD and Crohn's disease (CD). The gene expression profiles of PD (GSE6613) and CD (GSE119600) were downloaded from the Gene Expression Omnibus (GEO) database and were identified as the common differentially expressed genes (DEGs) between the two diseases. Next, analyses were performed, including functional enrichment analysis, a protein-protein interaction network, core genes identification, and clinical correlation analysis. As a result, 178 common DEGs (113 upregulated genes and 65 downregulated genes) were found between PD and CD. The functional analysis found that they were enriched in regulated exocytosis, immune response, and lipid binding. Twelve essential hub genes including BUB1B, BUB3, DLGAP5, AURKC, CBL, PCNA, RAF1, LYN, RPL39L, MRPL13, RSL24D1, and MRPS11 were identified from the PPI network by using cytoHubba. In addition, inflammatory and metabolic pathways were jointly involved in these two diseases. After verifying expression levels in an independent dataset (GSE99039), a correlation analysis with clinical features showed that LYN and RAF1 genes were associated with the severity of PD. In conclusion, our study revealed the common pathogenesis of PD and CD. These common pathways and hub genes may provide novel insights for mechanism research.

摘要

帕金森病(PD)是第二常见的神经退行性疾病,其发病机制仍未完全阐明。越来越多的证据表明,肠道是PD发病机制的潜在起源。最近的研究发现,炎症性肠病是帕金森病的一个危险因素,但其潜在机制仍不清楚。本研究的目的是进一步探讨PD与克罗恩病(CD)之间的分子机制。从基因表达综合数据库(GEO)下载了PD(GSE6613)和CD(GSE119600)的基因表达谱,并将其鉴定为两种疾病之间的共同差异表达基因(DEGs)。接下来,进行了功能富集分析、蛋白质-蛋白质相互作用网络分析、核心基因鉴定和临床相关性分析。结果,在PD和CD之间发现了178个共同的DEGs(113个上调基因和65个下调基因)。功能分析发现,它们在调节性胞吐作用、免疫反应和脂质结合方面富集。通过使用cytoHubba从蛋白质-蛋白质相互作用网络中鉴定出12个关键枢纽基因,包括BUB1B、BUB3、DLGAP5、AURKC、CBL、PCNA、RAF1、LYN、RPL39L、MRPL13、RSL24D1和MRPS11。此外,炎症和代谢途径共同参与了这两种疾病。在独立数据集(GSE99039)中验证表达水平后,与临床特征的相关性分析表明,LYN和RAF1基因与PD的严重程度相关。总之,我们的研究揭示了PD和CD的共同发病机制。这些共同的途径和枢纽基因可能为机制研究提供新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b866/9221146/ade192fb84ab/brainsci-12-00774-g001.jpg

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