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通过综合分析鉴定帕金森病的关键基因和通路。

Identification of key genes and pathways in Parkinson's disease through integrated analysis.

机构信息

Department of Neurology, Liaocheng People's Hospital, Liaocheng Clinical School of Taishan Medical University, Liaocheng, Shandong 252004, P.R. China.

出版信息

Mol Med Rep. 2017 Oct;16(4):3769-3776. doi: 10.3892/mmr.2017.7112. Epub 2017 Jul 31.

DOI:10.3892/mmr.2017.7112
PMID:28765971
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5646954/
Abstract

Parkinson's disease (PD) is a progressive, degene-rative neurological disease, typically characterized by tremors and muscle rigidity. The present study aimed to identify differe-ntially expressed genes (DEGs) between patients with PD and healthy patients, and clarify their association with additional biological processes that may regulate factors that lead to PD. An integrated analysis of publicly available Gene Expression Omnibus datasets of PD was performed. DEGs were identified between PD and normal blood samples. Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses, as well as protein‑protein interaction (PPI) networks were used to predict the functions of identified DEGs. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) was performed to validate the predicted expression levels of identified DEGs in whole blood samples obtained from patients with PD and normal healthy controls. A total of 292DEGs were identified between the PD and normal blood samples. Of these, 156 genes were significantly upregulated and 136 genes were significantly downregulated in PD samples following integrated analysis of four PD expression datasets. The 10 most upregulated and downregulated genes were used to construct a PPI network, where ubiquitin C‑terminal hydrolase L1 (UCHL1), 3‑phosphoinositide dependent protein kinase 1 (PDPK1) and protein kinase cAMP‑activated catalytic subunit β (PRKACB) demonstrated the highest connectivity in the network. DEGs were significantly enriched in amoebiasis, vascular smooth muscle contraction, and the Wnt and calcium signaling pathways. The expression levels of significant DEGs, UCHL1, PDPK1 and PRKACB were validated using RT‑qPCR analysis. The findings revealed that UCHL1 and PDPK1 were upregulated and PRKACB was downregulated in patients with PD when compared with normal healthy controls. In conclusion, the results indicate that the significant DEGs, including UCHL1, PDPK1 and PRKACB may be associated with the development of PD. In addition, these factors may be involved in various signaling pathways, including amoebiasis, vascular smooth muscle contraction and the Wnt and calcium signaling pathways.

摘要

帕金森病(PD)是一种进行性、退行性神经疾病,通常表现为震颤和肌肉僵硬。本研究旨在鉴定 PD 患者与健康患者之间的差异表达基因(DEGs),并阐明它们与可能调节导致 PD 的因素的其他生物过程的关联。对 PD 的公开可用基因表达综合分析。鉴定 PD 与正常血样之间的 DEGs。使用基因本体论富集和京都基因与基因组百科全书通路分析以及蛋白质-蛋白质相互作用(PPI)网络来预测鉴定的 DEGs 的功能。逆转录-定量聚合酶链反应(RT-qPCR)用于验证从 PD 患者和正常健康对照获得的全血样本中鉴定的 DEGs 的预测表达水平。在综合分析四个 PD 表达数据集后,在 PD 和正常血样之间鉴定了 292 个 DEGs。其中,156 个基因在 PD 样本中显著上调,136 个基因显著下调。使用 10 个上调和下调最显著的基因构建 PPI 网络,其中泛素 C 端水解酶 L1(UCHL1)、3-磷酸肌醇依赖性蛋白激酶 1(PDPK1)和蛋白激酶 cAMP 激活的催化亚基β(PRKACB)在网络中表现出最高的连通性。DEGs 在阿米巴病、血管平滑肌收缩和 Wnt 和钙信号通路中显著富集。使用 RT-qPCR 分析验证了显著 DEGs,UCHL1、PDPK1 和 PRKACB 的表达水平。结果表明,与正常健康对照组相比,PD 患者的 UCHL1 和 PDPK1 上调,PRKACB 下调。结论表明,包括 UCHL1、PDPK1 和 PRKACB 在内的显著 DEGs 可能与 PD 的发展有关。此外,这些因素可能参与各种信号通路,包括阿米巴病、血管平滑肌收缩以及 Wnt 和钙信号通路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99aa/5646954/3ac3cd406052/MMR-16-04-3769-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99aa/5646954/3c70ceced22c/MMR-16-04-3769-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99aa/5646954/9858490daa3c/MMR-16-04-3769-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99aa/5646954/3ac3cd406052/MMR-16-04-3769-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99aa/5646954/3c70ceced22c/MMR-16-04-3769-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99aa/5646954/9858490daa3c/MMR-16-04-3769-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99aa/5646954/3ac3cd406052/MMR-16-04-3769-g02.jpg

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