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.

Sequence Alignment between TRIM33 Gene and Human Noncoding RNAs: A Potential Explanation for Paraneoplastic Dermatomyositis

“…These results were then compared with those from previously published experimental studies on plasma or muscle samples from patients with DM or other IIMs [ 22 , 35 , 36 , 37 , 38 , 39 ]. As shown in Table 3 , a total of 28 correlations were found.…”

Sporadic Inclusion Body Myositis at the Crossroads between Muscle Degeneration, Inflammation, and Aging

“…Even though only a few patients were analyzed, and transcriptomic signatures of different IIM need to be confirmed in a higher number of patients, the study showed the feasibility and power of scRNAseq to investigate IIM [ 266 ]. The role of miRNA in sIBM has been recently exposed [ 267 , 268 ]. Analysis of miRNA expression profile in the skeletal muscle of patients with IIM using NanoString led to the identification of a specific miRNA signature in sIBM [ 267 ].…”

“…The role of miRNA in sIBM has been recently exposed [ 267 , 268 ]. Analysis of miRNA expression profile in the skeletal muscle of patients with IIM using NanoString led to the identification of a specific miRNA signature in sIBM [ 267 ]. miR-150-5p, a miRNA that regulates B- and T-cell differentiation, was found specifically increased in sIBM compared to healthy subjects and patients with other IIM and proposed as a possible biomarker for sIBM.…”

“…This finding agrees with the presence of highly differentiated T and B cells in sIBM muscles. Also, miRNA involved in muscle regeneration have been found to be increased in sIBM [ 267 ]. Machine learning techniques are also emerging as powerful tools to improve our understanding of the disease, discover new biomarkers of sIBM, and expose new potential therapeutic targets [ 269 ].…”

Transcriptome Analysis of miRNA and mRNA in Porcine Skeletal Muscle following Glaesserella parasuis Challenge

“…In many cases, miRNAs have been found to be involved in pathological and physiological stress [ 25 , 26 , 27 , 28 ]. Dysregulated expression of miRNAs in skeletal muscle-related diseases suggests their potential role in protecting or exacerbating skeletal muscle during disease [ 29 , 30 , 31 , 32 ]. Some miRNAs have been identified as non-invasive biomarkers for muscular dystrophy [ 33 ], while others have been shown to inhibit muscle atrophy and renal fibrosis or contribute to therapeutic protein restoration [ 34 , 35 , 36 ].…”