title: Altered let-7 expression in Myasthenia gravis and let-7c mediated regulation of IL-10 by directly targeting IL-10 in Jurkat cells.
abstract: Myasthenia gravis (MG) is a T cell-dependent and B cell-mediated autoimmune disease of neuromuscular junctions and cytokines may play a crucial role in the pathogenesis and perpetuation of MG. MicroRNAs (miRNAs) have been implicated as fine-tuning regulators controlling diverse biological processes at the level of posttranscriptional repression. Dysregulation of miRNAs has been described in various disease states. In this study, miRNA microarrays identified let-7 family to be decreased in peripheral blood mononuclear cells (PBMCs) from MG patients compared to the healthy controls. We next demonstrated the differential expression of let-7 family in larger samples by quantitative real-time PCR. Using a combination of bioinformatics and molecular approaches, we confirmed IL-10 as a target for let-7c. IL-10 expression also showed a negative correlation with let-7c expression in PBMCs from MG patients. Further experiments revealed that induced levels of IL-10 were inversely related to let-7c levels. We also showed that let-7c could regulate IL-10 expression in Jurkat cells. In summary, our results suggest that abnormal expression/regulation of microRNAs may contribute to or be indicative of the initiation and progression of MG.
authors: State Key Laboratory of Bioreactor Engineering & Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, PR China.
authors: Lin
authors: L
authors: Jiang
authors: Zhuoan
authors: Z
authors: Cheng
authors: Shaobo
authors: S
authors: Qiu
authors: Zujun
authors: Z
authors: Que
authors: Wenjing
authors: W
authors: Bao
authors: Chao
authors: C
authors: Jiang
authors: Fangyuan
authors: F
authors: Zou
authors: Ping
authors: P
authors: Liu
authors: Jianwen
authors: J
authors: Liu
mesh_terms: D019295:Computational Biology; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D019169:Jurkat Cells; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D046228:Microarray Analysis; D009157:Myasthenia Gravis / Q000235:genetics / Q000276:immunology*
chemical_list: D035683:MicroRNAs; C487931:mirnlet7 microRNA, human; D016753:Interleukin-10