Expression profiling and bioinformatics analysis of exosomal long noncoding RNAs in patients with myasthenia gravis by RNA sequencing

摘要

Background Myasthenia gravis (MG) is an autoimmune disease mediated by acetylcholine receptor antibodies. Exosomes were shown to be involved in the immune modulation and autoimmune diseases. However, the expression and function of exosomal long noncoding RNAs (lncRNAs) in MG are still unclear. Methods We conducted high‐throughput sequencing to detect the lncRNA profiles of serum exosomes in 6 MG patients (2 grade I, 2 grade IIa, and 2 grade IIb) and 6 healthy controls (HC). Then, differentially expressed (DE) lncRNAs with the greatest difference between the MG and HC groups were selected for further quantitative real‐time polymerase chain reaction (qRT‐PCR) validation in additional 30 MG patients and 10 HC. The DE lncRNAs were used to construct the coding/noncoding network and perform enrichment analysis. Results We identified 378 significantly upregulated and 348 significantly downregulated lncRNAs in MG patients compared with HC. The top 5 lncRNAs (NR_104677.1, ENST00000583253.1, NR_046098.1, NR_022008.1, and ENST00000581362.1) were validated and shown to be significantly increased in the serum exosome of MG, and the expression level of NR_046098.1 significantly increased with the MG grading. Enrichment analysis showed that DE genes mainly participated in the basic biological regulation of MG and immune‐related pathways, such as autoimmune thyroid disease pathway and T‐cell receptor signaling pathway. A specific lncRNA‐miRNA‐mRNA regulatory network associated with the 5 lncRNAs, 14 MG‐related miRNAs and 30 mRNAs was constructed. Conclusions We conducted a comprehensive analysis of exosomal lncRNAs to reveal potential biomarkers for the MG diagnosis and severity assessment.