长链非编码 RNA 表达谱的综合分析及 ENST00000604491 在 Graves 病中的潜在作用。
Comprehensive Analysis of lncRNA Expression Profile and the Potential Role of ENST00000604491 in Graves' Disease.
机构信息
Department of Endocrinology, The Affiliated People's Hospital of Jiangsu University, Zhenjiang Medical School of Nanjing Medical University, Zhenjiang 212002, China.
Department of Critical Care Medicine, The Affiliated People's Hospital of Jiangsu University, Zhenjiang Medical School of Nanjing Medical University, Zhenjiang 212002, China.
出版信息
J Immunol Res. 2022 Apr 25;2022:8067464. doi: 10.1155/2022/8067464. eCollection 2022.
BACKGROUND
Graves' disease (GD) is one of the most common autoimmune diseases worldwide and develops in 20 to 50 cases per 100,000 persons annually. Long noncoding RNAs (lncRNAs) are widely expressed in multiple human diseases and have pivotal functions in gene regulation. This study is aimed at determining the lncRNA profile in peripheral blood mononuclear cells (PBMCs) from GD patients and investigating the role of ENST00000604491 in GD.
METHODS
A total of 31 GD patients and 32 normal controls were enrolled in the study. Next-generation sequencing was performed to identify the dysregulated lncRNAs in the PBMCs from the 5 GD patients and 5 normal controls, and 26 GD patients and 27 controls were used to verify the selected lncRNAs. The relative expression of verified lncRNAs, forkhead box P1 (FOXP1), and IKAROS family zinc finger 3 (IKZF3) from these samples was detected by quantitative real-time PCR. The potential biomarker value was assessed by using receiver operating characteristic (ROC) curve analysis.
RESULTS
A total of 37,683 dysregulated expressed lncRNAs were indicated, of which 5 lncRNAs were significantly upregulated and 83 lncRNAs were remarkably downregulated in the GD patients compared with healthy subjects. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses showed that abnormally expressed lncRNAs were mainly enriched in immune system-related signalling pathways. Among the selected lncRNAs, the relative expression of ENST00000604491 was significantly downregulated and negatively correlated with the serum levels of thyroid-stimulating hormone receptor antibodies (TRAb) in GD patients. Further studies confirmed that decreased FOXP1 expression was inversely correlated with serum TRAb levels in GD patients. Moreover, there was a notably positive correlation between ENST00000604491 expression and FOXP1 transcript levels in GD. The area under the ROC curve of ENST00000604491 was up to 0.74 (95% confidence interval: 0.60-0.87, < 0.01), and the sensitivity and specificity were 53.85% and 88.89%, respectively.
CONCLUSION
The present study identifies ENST00000604491 as a significantly attenuated lncRNA in GD patients, which may contribute to the pathogenesis of GD by regulating FOXP1 and represent a potential biomarker for GD.
背景
格雷夫斯病（GD）是全球最常见的自身免疫性疾病之一，每年每 10 万人中有 20 至 50 例发病。长链非编码 RNA（lncRNA）广泛表达于多种人类疾病中，在基因调控中具有关键作用。本研究旨在确定 GD 患者外周血单个核细胞（PBMC）中的 lncRNA 谱，并研究 ENST00000604491 在 GD 中的作用。
方法
本研究共纳入 31 例 GD 患者和 32 例正常对照。对 5 例 GD 患者和 5 例正常对照的 PBMC 进行下一代测序，以鉴定失调的 lncRNA，并对 26 例 GD 患者和 27 例对照进行验证。采用实时定量 PCR 检测这些样本中验证的 lncRNA、叉头框 P1（FOXP1）和 IKAROS 家族锌指蛋白 3（IKZF3）的相对表达水平。采用受试者工作特征（ROC）曲线分析评估潜在的生物标志物价值。
结果
共发现 37683 个表达失调的 lncRNA，其中 5 个 lncRNA在 GD 患者中显著上调，83 个 lncRNA显著下调。基因本体论和京都基因与基因组百科全书通路分析表明，异常表达的 lncRNA 主要富集于免疫系统相关信号通路。在所选择的 lncRNA 中，ENST00000604491 的相对表达水平显著下调，并与 GD 患者血清促甲状腺素受体抗体（TRAb）水平呈负相关。进一步研究证实，GD 患者中 FOXP1 表达的降低与血清 TRAb 水平呈负相关。此外，ENST00000604491 的表达与 GD 患者 FOXP1 转录水平之间存在显著正相关。ENST00000604491 的 ROC 曲线下面积高达 0.74（95%置信区间：0.60-0.87， < 0.01），灵敏度和特异性分别为 53.85%和 88.89%。
结论
本研究鉴定出 ENST00000604491 是 GD 患者中显著下调的 lncRNA，它可能通过调节 FOXP1 而导致 GD 的发病机制，并可能成为 GD 的潜在生物标志物。
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