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类风湿关节炎患者外周血单个核细胞的网络分析与转录组分析

Network analysis and transcriptome profiling in peripheral blood mononuclear cells of patients with rheumatoid arthritis.

作者信息

Long Yan, Liu Jian, Jiang Hui, Xin Ling, Wan Lei, Sun Yue, Zhang Pingheng, Wen Jianting, Huang Dan, Sun Yanqiu, Zhang Ying, Bao Bingxi, Sun Guanghan

机构信息

Department of Graduate, Anhui University of Chinese Medicine, Hefei, Anhui 230011, P.R. China.

Laboratory for Rheumatism, Institute of Rheumatology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui 230011, P.R. China.

出版信息

Exp Ther Med. 2021 Feb;21(2):170. doi: 10.3892/etm.2020.9601. Epub 2020 Dec 25.

Abstract

The present study aimed to investigate the differential expression of long non-coding RNAs (lncRNAs) in rheumatoid arthritis (RA). High-throughput gene sequencing technology was used to detect the expression of lncRNA and mRNA in three patients with RA (RA group) and normal controls (NC group). A Bioinformatics analysis was used to assess the effects of differentially expressed mRNAs on signaling pathways and biological functions. The selected dysregulated lncRNAs were verified by reverse transcription-quantitative (RT-q)PCR in the peripheral blood mononuclear cells (PBMCs) of patients with RA and age- and sex-matched controls. A correlation analysis was used to analyze the relationship between lncRNAs and clinical indexes. From the lncRNA sequencing data, significantly differentially expressed lncRNAs between the RA and NC groups were identified by a fold change ≥2 and P<0.05. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis suggested that the differentially expressed mRNAs were mainly involved in organelle composition, intracellular regulation, signaling pathways, cancer, virus and inflammation. A total of four of these lncRNAs were confirmed by RT-qPCR to be significantly differentially expressed (LINC00304, MIR503HG, LINC01504 and FAM95B1). Through the correlation analysis, it was confirmed that there was a strong correlation between these lncRNAs and clinical laboratory indicators and indexes such as course of disease, arthrocele and joint tenderness. Overall, the present results suggested that the expression levels of LINC00304, MIR503HG, LINC01504 and FAM95B1 in PBMCs from patients with RA may serve as potential biomarkers for RA diagnosis, influencing the occurrence and progress of RA.

摘要

本研究旨在调查类风湿关节炎(RA)中长链非编码RNA(lncRNA)的差异表达。采用高通量基因测序技术检测3例RA患者(RA组)和正常对照(NC组)中lncRNA和mRNA的表达。利用生物信息学分析评估差异表达的mRNA对信号通路和生物学功能的影响。通过逆转录定量(RT-q)PCR在RA患者及年龄和性别匹配的对照者的外周血单个核细胞(PBMC)中验证所选失调的lncRNA。采用相关性分析来分析lncRNA与临床指标之间的关系。从lncRNA测序数据中,通过变化倍数≥2且P<0.05鉴定出RA组和NC组之间显著差异表达的lncRNA。基因本体论和京都基因与基因组百科全书分析表明,差异表达的mRNA主要参与细胞器组成、细胞内调节、信号通路、癌症、病毒和炎症。通过RT-qPCR证实这些lncRNA中有4种存在显著差异表达(LINC00304、MIR503HG、LINC01504和FAM95B1)。通过相关性分析,证实这些lncRNA与临床实验室指标以及病程、关节积液和关节压痛等指标之间存在强相关性。总体而言,目前的结果表明,RA患者PBMC中LINC00304、MIR503HG、LINC01504和FAM95B1的表达水平可能作为RA诊断的潜在生物标志物,影响RA的发生和进展。

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