Abstract
Objective: CD4+T cells are significant compositions of immune cells in rheumatoid arthritis (RA) and the aberrant function of CD4+T cells have been demonstrated to promote RA's progression. N6-methyladenosine (m6A) is a highly enriched modification found in CircRNAs. However, the role of m6A-methylated circRNA in regulation of CD4+T cells function in RA and its association with RA disease activity are presently unclear. Methods: We used m6A-circRNA epitranscriptomic microarray analysis and m6A RNA immunocoprecipitation-quantitative polymerase chain reaction (MeRIP-qPCR) to screen and verify the differentially expressed m6A-methylated circRNAs in CD4+T cells from RA and HC. Results: Many m6A-methylated circRNAs were differentially expressed in patients with new-onset RA. M6A-methylated circFOXK2 in the CD4+T cells of patients with new-onset RA was significantly decreased, the expression level of circFOXK2 in the CD4+T cells of patients with new-onset RA was significantly increased and correlated with treatment, Th17 %, autophagy. CircFOXK2 could function as competing endogenous RNAs to regulate miR-486-3p expression. In many m6A regulators, only a-ketoglutarate-dependent dioxygenase alkB homolog 5 (ALKBH5) was significantly increased in the CD4+T cells of patients with new-onset RA, and its level positively correlated with rheumatoid factor, the expression of circFOXK2. Moreover, the change of ALKBH5 could affect the level of m6A and circFOXK2 in Jurkat cell line. Conclusion: We indicated a notable decrease in the m6A-methylated level of circFOXK2 in CD4+T cells from human RA, indicating a potential role of hypomethylated circFOXK2 in CD4+T cells function and RA pathogenesis. This may show valuable insight into the ALKBH5/m6A-circFOXK2/miRNA interaction network and the mechanism of RA.