title: miR-15b is Downregulated in Myasthenia Gravis Patients and Directly Regulates the Expression of Interleukin-15 (IL-15) in Experimental Myasthenia Gravis Mice.
abstract: BACKGROUND
  miR-15b is significantly and consistently downregulated in different clinical phenotypes of myasthenia gravis (MG). However, its role in pathogenesis of MG is still not clear. This study aimed to explore the function of miR-15b in MG.
  
  
  METHODS
  Blood samples from early-onset MG, late-onset MG, thymoma patients, and healthy participants were collected. The expression pattern of IL-15 and miR-15b was identified by qRT-PCR and ELISA in patient serum and mouse tissue samples. The regulative role of miR-15b on IL-15 expression was verified in an experimental autoimmune myasthenia gravis (EAMG) mice model.
  
  
  RESULTS
  qRT-PCR and ELISA showed that miR-15b expression was significantly lower and IL-15 expression was significantly higher in all EMG, LMG, and thymoma cases compared to healthy controls. Based on mouse model, we confirmed that miR-15b knockdown could increase IL-15 expression in healthy mice, while miR-15b overexpression could inhibit IL-15 expression in EAMG mice. Through searching in bioinformatics databases, we identified a highly conserved consequential pairing between IL-15 and miR-15b. Subsequent dual luciferase assay further verified this match.
  
  
  CONCLUSIONS
  This study is the first to report the miR-15b-IL-15 axis can directly regulate IL15 expression, which helps to further explain the abnormal IL-15 expression in MG patients and the pathogenesis of MG.
authors.affiliation: Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China (mainland).
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.affiliation: Zhongnan University Xiangya Medical College, Xiangya, Hubei, China (mainland).
authors.forename: Tiantian
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China (mainland).
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China (mainland).
authors.forename: Yapei
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China (mainland).
authors.forename: Changdong
authors.initials: C
authors.lastname: Song
authors.affiliation: Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China (mainland).
authors.forename: Dandan
authors.initials: D
authors.lastname: Song
authors.affiliation: Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China (mainland).
authors.forename: Hengfang
authors.initials: H
authors.lastname: Liu
mesh_terms: D000818:Animals; D019295:Computational Biology; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000502:physiology*; D055785:Gene Knockdown Techniques; D006801:Humans; D019409:Interleukin-15 / Q000378:metabolism*; D008156:Luciferases; D051379:Mice; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D009157:Myasthenia Gravis / Q000097:blood / Q000503:physiopathology*; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D013945:Thymoma / Q000097:blood
chemical_list: D019409:Interleukin-15; C505361:MIRN15 microRNA, human; D035683:MicroRNAs; D008156:Luciferases