Department of Endocrinology & Rheumatology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, China.
Front Endocrinol (Lausanne). 2021 Sep 20;12:666393. doi: 10.3389/fendo.2021.666393. eCollection 2021.
Epigenetic modifications in RNA are known to play critical roles in cell differentiation through regulating expressions of some key genes including members of the suppressor of cytokine signaling (SOCS) family. The present study aimed to unveil the relationship of SOCS mRNA methylation induced by methyltransferase like 3 (METTL3) with Graves' disease (GD).
Differently expressed genes (DEG) in GD tissues were identified using microarray analysis and further validated using CD4 T cell microarray of GD tissues and isolated peripheral blood mononuclear cells (PBMCs). Furthermore, expressions of METTL3 targeted genes were detected using METTL3 knock-down experiment in RAW264.7 cells.
High throughput microarrays revealed that METTL3 and SOCS molecules were aberrantly expressed in thyroid tissues and CD4T cells of GD compared to the controls. Bioinformatic analysis was undertaken by searching databases of found genes of the SOCS family that possessed many mRNA m6A modification loci. METTL3 knock-down experiment revealed that expressions of SOCS family members SOCS1, SOCS2, SOCS4, SOCS5, and SOCS6 were increased after METTL3 knock-down.
For the first time, the present study revealed the relationship between m6A modification and GD and indicated that METTL3 may be involved in the development of GD by inducing mRNA m6A methylation modification of SOCS family members.
已知 RNA 中的表观遗传修饰通过调节一些关键基因（包括细胞因子信号转导抑制因子（SOCS）家族成员）的表达，在细胞分化中发挥关键作用。本研究旨在揭示甲基转移酶样 3（METTL3）诱导的 SOCS mRNA 甲基化与格雷夫斯病（GD）之间的关系。
使用微阵列分析鉴定 GD 组织中的差异表达基因（DEG），并使用 GD 组织和分离的外周血单核细胞（PBMC）的 CD4 T 细胞微阵列进一步验证。此外，在 RAW264.7 细胞中通过 METTL3 敲低实验检测 METTL3 靶向基因的表达。
高通量微阵列显示，与对照组相比，METTL3 和 SOCS 分子在甲状腺组织和 GD 的 CD4T 细胞中异常表达。通过搜索 SOCS 家族的发现基因数据库进行生物信息学分析，该数据库具有许多 mRNA m6A 修饰位点。METTL3 敲低实验显示，METTL3 敲低后 SOCS 家族成员 SOCS1、SOCS2、SOCS4、SOCS5 和 SOCS6 的表达增加。
本研究首次揭示了 m6A 修饰与 GD 之间的关系，并表明 METTL3 可能通过诱导 SOCS 家族成员的 mRNA m6A 甲基化修饰参与 GD 的发生。
