LncRNAs NR-026690 和 ENST00000447867 在 COPD 急性加重患者的 CD4 T 细胞中上调。
LncRNAs NR-026690 and ENST00000447867 are upregulated in CD4 T cells in patients with acute exacerbation of COPD.
机构信息
Department of Respiratory and Critical Care Medicine, Key Laboratory of Pulmonary Diseases of Health Ministry, Key Cite of National Clinical Research Center for Respiratory Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences & Technology, Wuhan, China,
出版信息
Int J Chron Obstruct Pulmon Dis. 2019 Mar 26;14:699-711. doi: 10.2147/COPD.S191815. eCollection 2019.
OBJECTIVE
The aim of the study was to determine the expression profile of long noncoding RNAs (lncRNAs) in CD4 T cells from COPD patients and explore the clinical value of the lncRNAs.
METHODS
First, microarray analysis was performed. Differentially expressed lncRNAs were validated by quantitative real-time reverse transcription-PCR (qRT-PCR) in samples from 56 patients with acute exacerbations of COPD (AECOPD), 56 patients with stable COPD, and 35 healthy controls. Meanwhile, the clinical value was tested by receiver operating characteristic curve analysis. The functions of lncRNAs were analyzed by the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes database. The potential target genes that might be regulated by NR-026690 and ENST00000447867 were identified by the lncRNA-mRNA network and competing endogenous RNA network. The transcriptional expression level of rap guanine nucleotide exchange factor 3 (RAPGEF3) was tested by qRT-PCR. The correlation of the expression between NR-026690, ENST00000447867, and RAPGEF3 was analyzed by Spearman's correlation test.
RESULTS
We found that the relative expression levels of ENST00000447867 and NR-026690 in the CD4 T cells of AECOPD patients were significantly higher than in the stable COPD patients and control subjects by microarray and qRT-PCR validation. The transcriptional expression level of RAPGEF3 in the CD4 T cells was significantly higher in the AECOPD group compared to the control group (<0.01) and the stable COPD group (<0.05). RAPGEF3 expression was positively associated with NR-026690 (=0.4925, <0.01) and ENST00000447867 (=0.4065, <0.01).
CONCLUSION
NR-026690 and ENST00000447867 might be potential biomarkers for COPD. They might affect RAPGEF3 as miRNA sponges to regulate COPD development.
目的
本研究旨在确定 COPD 患者 CD4 T 细胞中长链非编码 RNA（lncRNA）的表达谱，并探讨 lncRNA 的临床价值。
方法
首先进行微阵列分析。在 56 例 COPD 急性加重期（AECOPD）患者、56 例稳定期 COPD 患者和 35 例健康对照者的样本中，通过定量实时逆转录-PCR（qRT-PCR）验证差异表达的 lncRNA。同时，通过受试者工作特征曲线分析测试其临床价值。通过基因本体论和京都基因与基因组百科全书数据库分析 lncRNA 的功能。通过 lncRNA-mRNA 网络和竞争性内源 RNA 网络鉴定可能受 NR-026690 和 ENST00000447867 调节的潜在靶基因。通过 qRT-PCR 检测 rap 鸟嘌呤核苷酸交换因子 3（RAPGEF3）的转录表达水平。通过 Spearman 相关检验分析 NR-026690、ENST00000447867 和 RAPGEF3 之间的表达相关性。
结果
通过微阵列和 qRT-PCR 验证，我们发现 AECOPD 患者 CD4 T 细胞中 ENST00000447867 和 NR-026690 的相对表达水平明显高于稳定期 COPD 患者和对照组。CD4 T 细胞中 RAPGEF3 的转录表达水平在 AECOPD 组明显高于对照组（<0.01）和稳定期 COPD 组（<0.05）。RAPGEF3 表达与 NR-026690（=0.4925，<0.01）和 ENST00000447867（=0.4065，<0.01）呈正相关。
结论
NR-026690 和 ENST00000447867 可能是 COPD 的潜在生物标志物。它们可能通过作为 miRNA 海绵来影响 RAPGEF3 从而调节 COPD 的发生。
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