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利用生物信息学筛选与验证骨关节炎相关的枢纽基因

Screening and verification of hub genes involved in osteoarthritis using bioinformatics.

作者信息

Xie Junxiong, Deng Zhiqin, Alahdal Murad, Liu Jianquan, Zhao Zhe, Chen Xiaoqiang, Wang Guanghui, Hu Xiaotian, Duan Li, Wang Daping, Li Wencui

机构信息

Guangdong Provincial Research Center for Artificial Intelligence and Digital Orthopedic Technology, Hand and Foot Surgery Department, Shenzhen Second People's Hospital (The First Hospital Affiliated to Shenzhen University), Shenzhen, Guangdong 518000, P.R. China.

University of South China, School of Clinical Medicine, Hengyang, Hunan 421001, P.R. China.

出版信息

Exp Ther Med. 2021 Apr;21(4):330. doi: 10.3892/etm.2021.9761. Epub 2021 Feb 8.

DOI:10.3892/etm.2021.9761
PMID:33732303
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7903481/
Abstract

Osteoarthritis (OA) is one of the most common causes of disability and its development is associated with numerous factors. A major challenge in the treatment of OA is the lack of early diagnosis. In the present study, a bioinformatics method was employed to filter key genes that may be responsible for the pathogenesis of OA. From the Gene Expression Omnibus database, the datasets GSE55457, GSE12021 and GSE55325 were downloaded, which comprised 59 samples. Of these, 30 samples were from patients diagnosed with osteoarthritis and 29 were normal. Differentially expressed genes (DEGs) were obtained by downloading and analyzing the original data using bioinformatics. The Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathways were analyzed using the Database for Annotation, Visualization and Integrated Discovery online database. Protein-protein interaction network analysis was performed using the Search Tool for the Retrieval of Interacting Genes/proteins online database. BSCL2 lipid droplet biogenesis associated, seipin, FOS-like 2, activator protein-1 transcription factor subunit (FOSL2), cyclin-dependent kinase inhibitor 1A (CDKN1A) and kinectin 1 (KTN1) genes were identified as key genes by using Cytoscape software. Functional enrichment revealed that the DEGs were mainly accumulated in the ErbB, MAPK and PI3K-Akt pathways. Reverse transcription-quantitative PCR analysis confirmed a significant reduction in the expression levels of FOSL2, CDKN1A and KTN1 in OA samples. These genes have the potential to become novel diagnostic and therapeutic targets for OA.

摘要

骨关节炎(OA)是导致残疾的最常见原因之一,其发展与众多因素相关。OA治疗中的一个主要挑战是缺乏早期诊断。在本研究中,采用生物信息学方法筛选可能与OA发病机制相关的关键基因。从基因表达综合数据库下载了数据集GSE55457、GSE12021和GSE55325,这些数据集包含59个样本。其中,30个样本来自被诊断为骨关节炎的患者,29个为正常样本。通过使用生物信息学下载和分析原始数据获得差异表达基因(DEG)。使用在线数据库注释、可视化和综合发现数据库分析基因本体富集和京都基因与基因组百科全书通路。使用在线数据库检索相互作用基因/蛋白质的搜索工具进行蛋白质-蛋白质相互作用网络分析。通过Cytoscape软件将与BSCL2脂滴生物合成相关的丝氨酸蛋白酶抑制剂、FOS样2、活化蛋白-1转录因子亚基(FOSL2)、细胞周期蛋白依赖性激酶抑制剂1A(CDKN1A)和驱动蛋白1(KTN1)基因鉴定为关键基因。功能富集显示,DEG主要聚集在表皮生长因子受体(ErbB)、丝裂原活化蛋白激酶(MAPK)和磷脂酰肌醇-3激酶-蛋白激酶B(PI3K-Akt)通路中。逆转录定量聚合酶链反应分析证实,OA样本中FOSL2、CDKN1A和KTN1的表达水平显著降低。这些基因有可能成为OA新的诊断和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b940/7903481/e581f2b0178f/etm-21-04-09761-g04.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b940/7903481/985523b360f3/etm-21-04-09761-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b940/7903481/d7dc32305273/etm-21-04-09761-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b940/7903481/f6b4dbdd3dbd/etm-21-04-09761-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b940/7903481/e89a81d60d98/etm-21-04-09761-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b940/7903481/e581f2b0178f/etm-21-04-09761-g04.jpg

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PI3K/Akt inhibitor partly decreases TNF-α-induced activation of fibroblast-like synoviocytes in osteoarthritis.PI3K/Akt 抑制剂部分降低 TNF-α诱导的骨关节炎成纤维样滑膜细胞的激活。
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