Journal of neuroimmunology · 2026
A novel circ_0018483/miR-4310/ERRFI1 ceRNA axis in myasthenia gravis.
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Lv Jie, Liu Jing, Zhang Linyuan, Zhang Yingna, Zhang Jing, Zhao Xue, Yang Junhong, Guo Wei, Chen Shufan, Sun Zhan, Liu Ruichen, Zhang Mengdi, Liu Qian, Zhou Xinyue, Hu Jia, Dong Haiyan, Cui Xinxin, Gao Qingye, Gao Feng
Аннотация
BACKGROUND: Myasthenia gravis (MG) is one of the most prevalent disorder of the neuromuscular junction (NMJ). Non-coding RNAs regulate myoblast proliferation and differentiation.
METHODS: The differential expression of miRNAs was analysed by using RNA microarrays. Protein levels and gene expression were analysed by using Western blotting and quantitative real-time polymerase chain reaction. The interactions of miR-4310 with circ_0018483 or ERBB receptor feedback inhibitor 1 (ERRFI1) were assessed using dual-luciferase reporter assays. The expression and aggregation of acetylcholine receptors (AChRs) were observed and analysed by using immunofluorescence.
RESULTS: The expression of miR-4310 was downregulated in the whole blood of patients. circ_0018483 exhibited a sponge effect on miR-4310, and the inhibition of miR-4310 weakened AChR function. Additionally, miR-4310 targeted ERRFI1 and circ_0018483, and circ_0018483 affected the expression and aggregation of AChR by regulating miR-4310 and ERRFI1. circ_0018483 regulates the expression of ERRFI1 by targeting miR-4310, which in turn affects AChR expression and aggregation at the NMJ.
CONCLUSIONS: We confirmed a novel circ_0018483/miR-4310/ERRFI1 ceRNA axis in MG. Our findings suggest novel AChR regulation and MG molecular mechanisms research avenues.
METHODS: The differential expression of miRNAs was analysed by using RNA microarrays. Protein levels and gene expression were analysed by using Western blotting and quantitative real-time polymerase chain reaction. The interactions of miR-4310 with circ_0018483 or ERBB receptor feedback inhibitor 1 (ERRFI1) were assessed using dual-luciferase reporter assays. The expression and aggregation of acetylcholine receptors (AChRs) were observed and analysed by using immunofluorescence.
RESULTS: The expression of miR-4310 was downregulated in the whole blood of patients. circ_0018483 exhibited a sponge effect on miR-4310, and the inhibition of miR-4310 weakened AChR function. Additionally, miR-4310 targeted ERRFI1 and circ_0018483, and circ_0018483 affected the expression and aggregation of AChR by regulating miR-4310 and ERRFI1. circ_0018483 regulates the expression of ERRFI1 by targeting miR-4310, which in turn affects AChR expression and aggregation at the NMJ.
CONCLUSIONS: We confirmed a novel circ_0018483/miR-4310/ERRFI1 ceRNA axis in MG. Our findings suggest novel AChR regulation and MG molecular mechanisms research avenues.