Exploring the Roles of m6A-Modified circRNAs in Myasthenia Gravis Based on Multi-Omics Analysis

Myasthenia gravis (MG) is an autoimmune disease mediated by autoantibodies. The important roles of circRNAs modified by m6A methylation have been reported in the pathogenesis of other autoimmune diseases, but remain unclear in MG. To address this point, we collected peripheral blood mononuclear cells from six MG patients and six healthy controls and performed m6A‑circRNA epitranscriptomic microarray and RNA sequencing. Differentially m6A-modified circRNAs and differentially expressed genes (DEGs) were analyzed. A network was constructed containing 17 circRNAs, 30 miRNAs, and 34 DEGs. The GSE85452 dataset was downloaded. DEGs that were differentially expressed in the GSE85452 dataset were selected as seed genes. Finally, four candidate m6A-modified circRNAs (hsa_circ_0084735, hsa_circ_0018652, hsa_circ_0025731, and hsa_circ_0030997) were identified through a random walk with restart. We found that they had different degree correlations with different immune cells. The results of MeRIP-qPCR showed that the m6A methylated levels of hsa_circ_0084735 and hsa_circ_0025731 were downregulated in MG patients, while the other two circRNAs were not significantly different between MG and control group. For the first time, we explored the pathogenesis of MG at the epigenetic transcriptome level. Our results will open new perspectives for MG research and identify potential biomarkers and therapeutic targets for MG.