Identification of Unique microRNA Profiles in Different Types of Idiopathic Inflammatory Myopathy
Sandra Muñoz-Braceras,
Iago Pinal-Fernandez,
Maria Casal-Dominguez,
Katherine Pak,
José César Milisenda,
Shajia Lu,
Massimo Gadina,
Faiza Naz,
Gustavo Gutierrez-Cruz,
Stefania Dell’Orso,
Jiram Torres-Ruiz,
Josep Maria Grau-Junyent,
Albert Selva-O’Callaghan,
Julie J. Paik,
Jemima Albayda,
Lisa Christopher-Stine,
Thomas E. Lloyd,
Andrea M. Corse,
Andrew L. Mammen
Affiliations
Sandra Muñoz-Braceras
Muscle Disease Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Iago Pinal-Fernandez
Muscle Disease Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Maria Casal-Dominguez
Muscle Disease Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Katherine Pak
Muscle Disease Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
José César Milisenda
Muscle Disease Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Shajia Lu
Translational Immunology Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Massimo Gadina
Translational Immunology Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Faiza Naz
Genomic Technology Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Gustavo Gutierrez-Cruz
Genomic Technology Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Stefania Dell’Orso
Genomic Technology Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Jiram Torres-Ruiz
Muscle Disease Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Josep Maria Grau-Junyent
Muscle Research Unit, Internal Medicine Service, Hospital Clinic de Barcelona, 08036 Barcelona, Spain
Albert Selva-O’Callaghan
Systemic Autoimmune Diseases Unit, Vall d’Hebron General Hospital, Universitat Autònoma de Barcelona, 08035 Barcelona, Spain
Julie J. Paik
Division of Rheumatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Jemima Albayda
Division of Rheumatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Lisa Christopher-Stine
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Thomas E. Lloyd
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Andrea M. Corse
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Andrew L. Mammen
Muscle Disease Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
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.