Li Shuang, Zhang Yu, Liu Geyu, Song Na, Ruan Zhe, Guo Rongjing, Tang Yonglan, Cao Xiangqi, Huang Xiaoxi, Gao Ting, Hao Sijia, Wang Qingqing, Chang Ting
Department of Neurology, Tangdu Hospital, the Fourth Military Medical University, Xi'an, 710038, Shaanxi, China.
Department of Neurosurgery, Tangdu Hospital, the Fourth Military Medical University, Xi'an, 710038, Shaanxi, China.
Mol Neurobiol. 2025 Feb;62(2):1694-1704. doi: 10.1007/s12035-024-04352-9. Epub 2024 Jul 17.
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.
重症肌无力（MG）是一种由自身抗体介导的自身免疫性疾病。m6A甲基化修饰的环状RNA（circRNA）在其他自身免疫性疾病的发病机制中发挥的重要作用已有报道，但在MG中仍不清楚。为了解决这一问题，我们收集了6例MG患者和6例健康对照者的外周血单个核细胞，并进行了m6A-circRNA表观转录组微阵列和RNA测序。分析了差异m6A修饰的circRNA和差异表达基因（DEG）。构建了一个包含17个circRNA、30个miRNA和34个DEG的网络。下载了GSE85452数据集。选择在GSE85452数据集中差异表达的DEG作为种子基因。最后，通过带重启的随机游走鉴定出4个候选的m6A修饰的circRNA（hsa_circ_0084735、hsa_circ_0018652、hsa_circ_0025731和hsa_circ_0030997）。我们发现它们与不同免疫细胞具有不同程度的相关性。MeRIP-qPCR结果显示，MG患者中hsa_circ_0084735和hsa_circ_0025731的m6A甲基化水平下调，而另外两个circRNA在MG组和对照组之间无显著差异。我们首次在表观转录组水平上探索了MG的发病机制。我们的结果将为MG研究开辟新的视角，并为MG鉴定潜在的生物标志物和治疗靶点。
