Identification of Unique microRNA Profiles in Different Types of Idiopathic Inflammatory Myopathy

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.