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

Fanfan Xu1, Xiaotong Kong1, Shanshan Peng1

  • 1Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.

Insights

Circular RNA NUP214 (circNUP214) is elevated in myasthenia gravis (MG) patients, promoting T cell proliferation by regulating miR-31 and NFAT5. This finding reveals a potential therapeutic target for MG.

Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • Myasthenia gravis (MG) is an autoimmune neuromuscular junction disorder.
  • Circular RNAs (circRNAs) are implicated in MG, but their specific roles are unclear.
  • The function of circNUP214 in MG pathogenesis has not been previously investigated.

Purpose of the Study:

  • To investigate the expression and function of circNUP214 in patients with acetylcholine receptor (AChR) antibody-positive myasthenia gravis.
  • To elucidate the regulatory mechanism of circNUP214 involving miR-31 and NFAT5 in CD4+ T cells.

Main Methods:

  • Quantitative real-time PCR (qRT-PCR) to measure circNUP214 expression in peripheral blood mononuclear cells (PBMCs) and CD4+ T cells.
  • Verification of circNUP214's structure and localization.
  • Confirmation of circNUP214 interaction with miR-31 and assessment of its effect on CD4+ T cell proliferation.
  • Rescue experiments in Jurkat cells to validate the circNUP214/miR-31/NFAT5 ceRNA axis.

Main Results:

  • circNUP214 expression was significantly higher in PBMCs and CD4+ T cells of MG patients compared to healthy controls.
  • circNUP214 promoted CD4+ T cell proliferation, while its knockdown inhibited this effect.
  • circNUP214 directly binds to miR-31, upregulating NFAT5 expression by sponging miR-31, forming a ceRNA regulatory axis.

Conclusions:

  • circNUP214 is upregulated in AChR-positive MG patients and contributes to aberrant CD4+ T cell proliferation.
  • The circNUP214/miR-31/NFAT5 axis represents a novel regulatory pathway in MG pathogenesis.
  • circNUP214 may serve as a potential diagnostic biomarker or therapeutic target for myasthenia gravis.

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