Yin Qinglei, Jin Zhou, Zhou Yulin, Song Dalong, Fu Chenyang, Huang FengJiao, Wang Shu
Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Endocr Connect. 2020 Dec;9(12):1202-1211. doi: 10.1530/EC-20-0373.
Graves' disease (GD) is a common autoimmune disease that affects the thyroid gland. As a new class of modulators of gene expression, long noncoding RNAs (lncRNAs) have been reported to play a vital role in immune functions and in the development of autoimmunity and autoimmune disease. The aim of this study is to identify lncRNAs in CD4+ T cells as potential biomarkers of GD. lncRNA and mRNA microarrays were performed to identify differentially expressed lncRNAs and mRNAs in GD CD4+ T cells compared with healthy control CD4+ T cells. Quantitative PCR (qPCR) was used to validate the results, and correlation analysis was used to analyze the relationship between these aberrantly expressed lncRNAs and clinical parameters. The microarray identified 164 lncRNAs and 93 mRNAs in GD CD4+ T cells differentially expressed compared to healthy control CD4+ T cells (fold change >2.0 and a P < 0.05). Further analysis consistently showed that the expression of HMlincRNA1474 (P < 0.01) and TCONS_00012608 (P < 0.01) was suppressed, while the expression of AK021954 (P < 0.01) and AB075506 (P < 0.01) was upregulated from initial GD patients. In addition, their expression levels were recovered in euthyroid GD patients and GD patients in remission. Moreover, these four aberrantly expressed lncRNAs were correlated with GD clinical parameters. Moreover, the areas under the ROC curve were 0.8046, 0.7579, 0.8115 for AK021954, AB075506, HMlincRNA1474, respectively. The present work revealed that differentially expressed lncRNAs were associated with GD, which might serve as novel biomarkers of GD and potential targets for GD treatment.
格雷夫斯病（GD）是一种常见的自身免疫性疾病，会影响甲状腺。作为一类新的基因表达调节剂，长链非编码RNA（lncRNAs）已被报道在免疫功能以及自身免疫和自身免疫性疾病的发展中发挥至关重要的作用。本研究的目的是鉴定CD4+T细胞中的lncRNAs作为GD的潜在生物标志物。进行lncRNA和mRNA微阵列分析以鉴定GD CD4+T细胞与健康对照CD4+T细胞相比差异表达的lncRNAs和mRNAs。采用定量PCR（qPCR）验证结果，并进行相关性分析以分析这些异常表达的lncRNAs与临床参数之间的关系。微阵列分析确定，与健康对照CD4+T细胞相比，GD CD4+T细胞中有164个lncRNAs和93个mRNAs差异表达（倍数变化>2.0且P<0.05）。进一步分析一致显示，初发GD患者中HMlincRNA1474（P<0.01）和TCONS_00012608（P<0.01）的表达受到抑制，而AK021954（P<0.01）和AB075506（P<0.01）的表达上调。此外，在甲状腺功能正常的GD患者和缓解期GD患者中，它们的表达水平恢复正常。此外，这四个异常表达的lncRNAs与GD临床参数相关。此外，AK021954、AB075506、HMlincRNA1474的ROC曲线下面积分别为0.8046、0.7579、0.8115。目前的研究表明，差异表达的lncRNAs与GD相关，可能作为GD的新型生物标志物和GD治疗的潜在靶点。
