AUTHOR=Song Rong-hua , Du Peng , Gao Chao-qun , Liu Xue-rong , Zhang Jin-an 

TITLE=METTL3 Is Involved in the Development of Graves’ Disease by Inducing SOCS mRNA m6A Modification

JOURNAL=Frontiers in Endocrinology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2021.666393

DOI=10.3389/fendo.2021.666393

ISSN=1664-2392

ABSTRACT=Objective: Epigenetic modifications in RNA is well-known to exert critical roles in cell differentiation through regulating expressions of some key genes including members of 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). 
Methods: 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.  
Results: High throughput microarrays revealed that METTL3 and SOCS molecules were aberrantly expressed in thyroid tissues and CD4+T cells of GD compared to the controls. Bioinformatic analysis by searching database found genes of SOCS family possessed many mRNA m6A modification loci. METTL3 knock-down experiment revealed that expressions of SOCS family members SOCS1, SOCS2, SOCS4, SOCS5 and SOCS6 were obviously increased after METTL3 knock-down.
Conclusions: Our present study for the first time revealed the relationship between m6A modification and GD and indicated that METTL3 may involve in the development of GD by inducing mRNA m6A methylation modification of SOCS family members.