Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
Sci Rep. 2024 Jun 12;14(1):13545. doi: 10.1038/s41598-024-64415-8.
The primary objective of this study is to understand the regulatory role of epigenetics in thyroid-associated ophthalmopathy (TAO) using multi-omics sequencing data. We utilized tRFs sequencing data, DNA methylation sequencing data, and lncRNA/circRNA/mRNA sequencing data, as well as several RNA methylation target prediction websites, to analyze the regulatory effect of DNA methylation, non-coding RNA, and RNA methylation on TAO-associated genes. Through differential expression analysis, we identified 1019 differentially expressed genes, 985 differentially methylated genes, and 2601 non-coding RNA. Functional analysis showed that differentially expressed genes were mostly associated with the PI3K signaling pathway and the IL17 signaling pathway. Genes regulated by DNA epigenetic regulatory networks were mainly related to the Cytokine-cytokine receptor interaction pathway, whereas genes regulated by RNA epigenetic regulatory networks were primarily related to the T cell receptor signaling pathway. Finally, our integrated regulatory network analysis revealed that epigenetics mainly impacts the occurrence of TAO through its effects on key pathways such as cell killing, cytokine production, and immune response. In summary, this study is the first to reveal a new mechanism underlying the development of TAO and provides new directions for future TAO research.
本研究的主要目的是利用多组学测序数据来理解表观遗传学在甲状腺相关性眼病（TAO）中的调控作用。我们利用 tRFs 测序数据、DNA 甲基化测序数据、lncRNA/circRNA/mRNA 测序数据，以及几个 RNA 甲基化靶标预测网站，分析了 DNA 甲基化、非编码 RNA 和 RNA 甲基化对 TAO 相关基因的调控作用。通过差异表达分析，我们鉴定了 1019 个差异表达基因、985 个差异甲基化基因和 2601 个非编码 RNA。功能分析表明，差异表达基因主要与 PI3K 信号通路和 IL17 信号通路相关。受 DNA 表观遗传调控网络调控的基因主要与细胞因子-细胞因子受体相互作用通路相关，而受 RNA 表观遗传调控网络调控的基因主要与 T 细胞受体信号通路相关。最后，我们的综合调控网络分析表明，表观遗传学主要通过对细胞杀伤、细胞因子产生和免疫反应等关键通路的影响来影响 TAO 的发生。总之，本研究首次揭示了 TAO 发生的新机制，为未来 TAO 的研究提供了新的方向。
