Li Yang, Huang Chengcheng, Yang Zhenguo, Wang Lei, Luo Dan, Qi Lu, Li Zhichao, Huang Yanqin
Department of orthopedics, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250000, China.
Department of Endocrinology and Metabology, The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250000, China.
Eur J Pharm Sci. 2022 Jun 1;173:106180. doi: 10.1016/j.ejps.2022.106180. Epub 2022 Apr 1.
Gout is a widespread inflammatory arthritis. The present study aimed to identify potential biomarkers of gout and explore their underlying mechanisms through bioinformatics methods.
The microarray data was downloaded from the GSE160170 dataset from the Gene Expression Omnibus (GEO) database, and the GEO2R online tool was used to obtain differentially expressed genes (DEGs). We searched for gout-related genes through the DisGeNET and GeneCards databases, and the final DEGs was acquired by intersection with the DEGs obtained from the microarray dataset. Tissue- and organ-specific genes were identified by the BioGPS online tool. Enrichment analysis was performed using GSEA4.1.0 and KOBAS3.0, and a protein-protein interaction (PPI) network was constructed using STRING to understand the biological functions and enrichment pathways of the DEGs as well as to identify their hub genes. Cytoscape was used to construct the competitive endogenous RNA (ceRNA) networks.
A total of 653 differentially expressed lncRNAs (DElncRNAs) and 818 differentially expressed mRNAs (DEmRNAs) were identified in the present study. After intersecting the differential DEGs from the dataset, 85 DEGs were obtained. Enrichment analyses showed that the DEGs were mainly enriched in the following biological processes (BPs): inflammation and regulation; immune response; and cell proliferation and apoptosis. Moreover, the DEGs were mainly enriched in rheumatoid arthritis (RA), osteoclast differentiation, interleukin (IL)-17 signaling pathway, nuclear factor kappa B (NF-κB) signaling pathway, Toll-like receptor signaling pathway and tumor necrosis factor (TNF) signaling pathway. Cytoscape software identified 15 hub genes, and the following 9 hub genes were obtained after intersecting with genes specifically expressed in the blood/immune and bone/muscle systems: TNF, JUN, PTGS2, STAT1, IL6, FOS, IL1β, CXCL8 and CD80. In addition, the lncRNA-NEAT1-miR-142-3p-IL-6 pathway may be a key regulatory pathway in the pathogenesis of gout.
The present study indicated that the identified 9 hub genes may be potential biomarkers for the diagnosis and treatment of gout. In addition, the results suggested that the lncRNA-NEAT1-miR-142-3p-IL-6 pathway may be a potential RNA regulatory pathway that controls the progression of gout disease.
痛风是一种常见的炎性关节炎。本研究旨在通过生物信息学方法鉴定痛风的潜在生物标志物并探索其潜在机制。
从基因表达综合数据库（GEO）的GSE160170数据集中下载微阵列数据，并使用GEO2R在线工具获取差异表达基因（DEG）。我们通过DisGeNET和GeneCards数据库搜索痛风相关基因，并通过与从微阵列数据集中获得的DEG进行交集来获得最终的DEG。使用BioGPS在线工具鉴定组织和器官特异性基因。使用GSEA4.1.0和KOBAS3.0进行富集分析，并使用STRING构建蛋白质-蛋白质相互作用（PPI）网络，以了解DEG的生物学功能和富集途径，并鉴定其枢纽基因。使用Cytoscape构建竞争性内源性RNA（ceRNA）网络。
本研究共鉴定出653个差异表达的长链非编码RNA（DElncRNA）和818个差异表达的信使核糖核酸（DEmRNA）。在将数据集中的差异DEG进行交集后，获得了85个DEG。富集分析表明，DEG主要富集于以下生物学过程（BP）：炎症与调节；免疫反应；以及细胞增殖和凋亡。此外，DEG主要富集于类风湿性关节炎（RA）、破骨细胞分化、白细胞介素（IL）-17信号通路、核因子κB（NF-κB）信号通路、Toll样受体信号通路和肿瘤坏死因子（TNF）信号通路。Cytoscape软件鉴定出15个枢纽基因，在与血液/免疫和骨骼/肌肉系统中特异性表达的基因进行交集后，获得了以下9个枢纽基因：TNF、JUN、PTGS2、STAT1、IL6、FOS、IL1β、CXCL8和CD80。此外，lncRNA-NEAT1-miR-142-3p-IL-6通路可能是痛风发病机制中的关键调控通路。
本研究表明，鉴定出的9个枢纽基因可能是痛风诊断和治疗的潜在生物标志物。此外，结果表明lncRNA-NEAT1-miR-142-3p-IL-6通路可能是控制痛风疾病进展的潜在RNA调控通路。
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