PDF(Pubmed)
Abstract：
Dermatomyositis (DM), antisynthetase syndrome (AS), immune-mediated necrotizing myopathy (IMNM), and inclusion body myositis (IBM) are four major types of idiopathic inflammatory myopathy (IIM). Muscle biopsies from each type of IIM have unique transcriptomic profiles. MicroRNAs (miRNAs) target messenger RNAs (mRNAs), thereby regulating their expression and modulating transcriptomic profiles. In this study, 18 DM, 12 IMNM, 6 AS, 6 IBM, and 6 histologically normal muscle biopsies underwent miRNA profiling using the NanoString nCounter system. Eleven miRNAs were exclusively differentially expressed in DM compared to controls, seven miRNAs were only differentially expressed in AS, and nine miRNAs were specifically upregulated in IBM. No differentially expressed miRNAs were identified in IMNM. We also analyzed miRNA-mRNA associations to identify putative targets of differentially expressed miRNAs. In DM and AS, these were predominantly related to inflammation and cell cycle progression. Moreover, our analysis showed an association between miR-30a-3p, miR-30e-3p, and miR-199b-5p downregulation in DM and the upregulation of target genes induced by type I interferon. In conclusion, we show that muscle biopsies from DM, AS, and IBM patients have unique miRNA signatures and that these miRNAs might play a role in regulating the expression of genes known to be involved in IIM pathogenesis.
摘要：
皮肌炎(DM),抗合成酶综合征（AS），免疫介导性坏死性肌病（IMNM），包涵体肌炎（IBM）是特发性炎症性肌病（IIM）的四种主要类型。来自每种类型的IIM的肌肉活检具有独特的转录组特征。微小RNA（miRNA）靶信使RNA（mRNA），从而调节它们的表达和调节转录组概况。在这项研究中,18DM,12IMNM,6AS,6IBM,使用NanoStringnCounter系统对6例组织学正常的肌肉活检进行了miRNA分析。与对照相比，11种miRNA在DM中唯一差异表达，七个miRNA仅在AS中差异表达，9个miRNA在IBM中被特异性上调。在IMNM中未鉴定出差异表达的miRNA。我们还分析了miRNA-mRNA关联以鉴定差异表达miRNA的推定靶标。在DM和AS中，这些主要与炎症和细胞周期进展有关.此外，我们的分析显示miR-30a-3p，miR-30e-3p,和miR-199b-5p在DM中的下调和I型干扰素诱导的靶基因上调。总之,我们显示来自DM的肌肉活检，AS,和IBM患者具有独特的miRNA特征，并且这些miRNA可能在调节已知与IIM发病机制有关的基因的表达中发挥作用。
