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Plasma exosomal RNAs has potential as both clinical biomarkers and therapeutic targets of dermatomyositis.

OBJECTIVES
Dermatomyositis (DM) is characterized by skeletal muscle weakness and cutaneous manifestations. Plasma exosomes (EXOs) contain proteins, RNAs, DNA, and lipid cargoes and are transferred among cells. Deeply investigated plasma EXO RNAs potentially improve our understanding of DM pathogenesis. We aimed to identify new potential biomarkers and therapeutic targets of DM.


METHODS
The RNAs (mRNA, miRNA and lncRNA) profiles of plasma EXOs were evaluated by sequencing on the Illumina HiSeq 3000 platform. Differentially expressed (DE) RNAs and bioinformatic analyses were performed. Human skeletal muscle myoblasts (HSkMCs) were stimulated with plasma EXOs, rapamycin or IFN-β. Real-time PCR and western blot were used to detect related genes and proteins.


RESULTS
A total of 689 DE mRNAs, 53 DE miRNAs and 452 DE lncRNAs were identified in DM plasma EXOs. Bioinformatic analysis inferred that plasma EXOs were secreted mainly by CD8+ T cells, regulatory T cells and natural killer cells. The DE miRNAs participated in the autophagy, TGF-β and Wnt signalling pathways. Three DE miRNAs (hsa-miR-125a-3p, hsa-miR-1246 and hsa-miR-3614-5p) were correlated with serological indices, organs involvement and myositis-specific autoantibodies. The DE lncRNAs participated in autophagy, interferon-β production and mTOR signalling. DM plasma EXOs can induce autophagy in HSkMCs by regulating 3 miRNAs (hsa-miR-125a-3p, hsa-miR-1246 and hsa-miR-3614-5p) and 3 lncRNAs (ENST00000584157.1, ENST00000523380.1, and ENST00000560054.1), which formed an autophagy network, playing the muscle damage roles.


CONCLUSIONS
Our study provides an overview of distinct RNAs profiles in DM plasma EXOs, and verified some miRNAs as potential biomarkers and therapeutic targets. The findings provide important clues for more in-depth explorations of plasma EXOs in DM.