Microarray profile of B cells from Graves' disease patients reveals biomarkers of proliferation
Microarray profile of B cells from Graves' disease patients reveals biomarkers of proliferation
复制标题
格雷夫斯病患者 B 细胞的微阵列图谱揭示了增殖的生物标志物
DOI：
10.1530/ec-20-0045
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发表时间：
2020-05-01
影响因子：
2.9
通讯作者：
Zha, Bingbing
中科院分区：
文献类型：
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作者：
Jiang, Xuechao;Wang, Yonghui;Zha, Bingbing
B 淋巴细胞是格雷夫斯病 (GD) 中促甲状腺激素受体 (TSHR) 自身抗体的来源。自身免疫 B 细胞表达谱的表征可能有助于更好地了解 GD 发病机制。为了揭示这一点，我们使用微阵列比较了新诊断GD患者和健康个体的纯化B细胞中长非编码RNA（lncRNA）和mRNA（基因）的表达水平，阐明了604个差异表达lncRNA（DE-lncRNA）和410个差异表达基因（DEG）。 GO和通路分析表明DEGs主要参与免疫反应。蛋白质-蛋白质相互作用网络呈现了经过实验验证的 DEG 之间的相互作用。使用两种独立的算法来识别调节 DEG 的 DE-lncRNA。对失调的 lncRNA-mRNA 对进行功能注释，确定了 14 对与细胞增殖相关的 mRNA。 lncRNA TCON_00022357-XLOC_010919 和 n335641 预计调节 TCL1 家族 AKT 共激活因子 A (TCL1A)，lncRNA n337845 预计调节含有 1A 的 SH2 结构域 (SH2D1A)。 TCL1A 和 SH2D1A 高度参与 B 细胞增殖。通过 qRT-PCR 验证了两个基因的差异表达。总之，GD 患者 B 细胞的 lncRNA 和 mRNA 表达谱表明，lncRNA-mRNA 对 n335641-TCL1A、TCONS-00022357-XLOC_010919-TCL1A 和 n337845-SH2D1A 可能通过调节 B 细胞增殖和存活来参与 GD 发病机制。因此，鉴定出的lncRNA和mRNA可能代表GD的新生物标志物和治疗靶点。
B lymphocytes are the source of autoantibodies against the thyroid-stimulating hormone receptor (TSHR) in Graves' disease (GD). Characterization of autoimmune B-cell expression profiles might enable a better understanding of GD pathogenesis. To reveal this, the expression levels of long noncoding RNAs (lncRNAs) and mRNAs (genes) in purified B cells from patients with newly diagnosed GD and healthy individuals were compared using microarrays, which elucidated 604 differentially expressed lncRNAs (DE-lncRNAs) and 410 differentially expressed genes (DEGs). GO and pathway analyses revealed that the DEGs are mainly involved in immune response. A protein-protein interaction network presented experimentally validated interactions among the DEGs. Two independent algorithms were used to identify the DE-lncRNAs that regulate the DEGs. Functional annotation of the deregulated lncRNA-mRNA pairs identified 14 pairs with mRNAs involved in cell proliferation. The lncRNAs TCON_00022357-XLOC_010919 and n335641 were predicted to regulate TCL1 family AKT coactivator A (TCL1A), and the lncRNA n337845 was predicted to regulate SH2 domain containing 1A (SH2D1A). TCL1A and SH2D1A are highly involved in B-cell proliferation. The differential expression of both genes was validated by qRT-PCR. In conclusion, lncRNA and mRNA expression profiles of B cells from patients with GD indicated that the lncRNA-mRNA pairs n335641-TCL1A, TCONS-00022357-XLOC_010919-TCL1A, and n337845-SH2D1A may participate in GD pathogenesis by modulating B-cell proliferation and survival. Therefore, the identified lncRNA and mRNA may represent novel biomarkers and therapeutic targets for GD.