Circular RNA circNUP214 serves as a microRNA-31 sponge to promote the progression of myasthenia gravis through NFAT5

Abstract

Myasthenia gravis (MG) is an autoimmune disease driven by autoantibodies targeting the neuromuscular junction, leading to muscle weakness. Although emerging evidence implicates circular RNAs (circRNAs) in MG, their specific regulatory mechanisms remain largely unknown. In particular, the role of circNUP214 in MG has not been characterized. CircNUP214 expression in PBMCs and CD4+ T cells from MG patients and healthy controls was determined by qRT-PCR. Its circular structure and cytoplasmic localization were verified. Furthermore, the interaction between circNUP214 and miR-31 was confirmed, and the regulatory effect of circNUP214 on CD4+ T cell proliferation was evaluated. In 31 pure AChR antibody-positive MG patients, circNUP214 expression was significantly elevated in PBMCs compared with healthy controls (HC). Elevated circNUP214 expression was also observed in CD4+ T cells. Functionally, circNUP214 promoted CD4+ T cell proliferation, while its knockdown suppressed this process. Mechanistically, circNUP214 directly bound miR-31 and upregulated NFAT5 via sponging miR-31. Rescue experiments in Jurkat cells further validated the circNUP214/miR-31/NFAT5 ceRNA regulatory axis. In conclusion, circNUP214 is highly expressed in PBMCs from 31 pure AChR antibody positive MG patients and is also elevated in CD4+ T cells. It upregulates NFAT5 expression by sponging miR-31 to promote proliferation. These findings suggest that the circNUP214/miR-31/NFAT5 axis may contribute to aberrant CD4+ T cell proliferation in MG.