Long non-coding RNA growth arrest specific 5 regulates the T helper 17/regulatory T balance by targeting miR-23a in myasthenia gravis

• Published in: Journal of international medical research Vol. 50; no. 6; p. 3000605211053703
• Main Authors: Xu, Yingying, Ouyang, Yiqun
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01-06-2022; Sage Publications Ltd; SAGE Publishing
• Subjects: Humans; Lymphocytes; MicroRNAs - genetics; MicroRNAs - metabolism; Myasthenia gravis; Myasthenia Gravis - genetics; Pre-Clinical Research Report; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Th17 Cells; growth arrest specific 5; Myasthenia gravis; T helper 17; CD4+ T cell; miR-23a; long non-coding RNA; regulatory T cell
• ISSN: 0300-0605; 1473-2300
• DOI: 10.1177/03000605211053703

Objective
Myasthenia gravis (MG) is a chronic autoimmune neuromuscular disorder. Recent studies report that long non-coding RNAs (lncRNAs) play vital roles in the pathogenesis of various diseases. This study explored the molecular mechanism of lncRNA growth arrest specific 5 (GAS5) in regulating the T helper 17 (Th17)/regulatory T (Treg) cell balance in MG.
Methods
GAS5 and miR-23a expression levels were detected by quantitative reverse transcription polymerase chain reaction. Flow cytometry was performed to examine the proportion of Th17 and Treg cells in CD4+ T cells from MG patients. The interaction between GAS5 and miR-23a was verified by luciferase reporter and RNA immunoprecipitation assays. Levels of Th17 and Treg-related proteins were examined using western blots and enzyme-linked immunosorbent assays.
Results
GAS5 expression levels were significantly decreased in the CD4+ T cells of MG patients, and GAS5 overexpression restrained Th17 differentiation in CD4+ T cells. Moreover, miR-23a was confirmed as a downstream target of GAS5 and negatively regulated by GAS5 through a direct interaction. Further exploration showed that GAS5 can inhibit Th17 differentiation by downregulating miR-23a.
Conclusion
Collectively, our results indicate that GAS5 can regulate the Th17/Treg balance by targeting miR-23a expression, providing a scientific basis for clinical therapeutic development for MG.