title: MicroRNA-10a Regulation of Proinflammatory Mediators: An Important Component of Untreated Juvenile Dermatomyositis.
abstract: OBJECTIVE
  To identify differentially expressed microRNA (miRNA) in muscle biopsies (MBx) from 15 untreated children with juvenile dermatomyositis (JDM) compared with 5 controls.
  
  
  METHODS
  Following MBx miRNA profiling, differentially expressed miRNA and their protein targets were validated by quantitative real-time PCR (qRT-PCR) and immunological assay. The association of miRNA-10a and miRNA-10b with clinical data was evaluated, including Disease Activity Score (DAS), von Willebrand factor antigen (vWF:Ag), nailfold capillary end row loops, duration of untreated disease, and tumor necrosis factor (TNF)-α-308A allele.
  
  
  RESULTS
  In JDM, 16/362 miRNA were significantly differentially expressed [false discovery rate (FDR) < 0.05]. Among these, miRNA-10a was the most downregulated miRNA in both FDR and ranking of fold change: miRNA-10a = -2.27-fold, miRNA-10b = -1.80-fold. Decreased miRNA-10a and miRNA-10b expressions were confirmed using q
  -4.16 and -2.59 fold, respectively. The qRT-PCR documented that decreased miRNA-10a expression was related to increased vascular cell adhesion molecule 1 in 13 of these JDM cases (correlation -0.67, p = 0.012), unlike miRNA-10b data (not significant). Concurrent JDM plasma contained increased levels of interleukin (IL) 6 (p = 0.0363), IL-8 (p = 0.0005), TNF-α (p = 0.0011), and monocyte chemoattractant proteins 1 (p = 0.0139). Decreased miRNA-10a, but not miRNA-10b, was associated with the TNF-α-308A allele (p = 0.015). In the 15 JDM, a trend of association of miRNA-10a (but not miRNA-10b) with vWF:Ag and DAS was observed.
  
  
  CONCLUSIONS
  MiRNA-10a downregulation is an important element in untreated JDM muscle pathophysiology. We speculate that muscle miRNA expression in adult dermatomyositis differs from muscle miRNA expression in untreated childhood JDM.
authors.affiliation: From the Stanley Manne Children's Research Institute; Ann and Robert H. Lurie Children's Hospital of Chicago; Department of Pediatrics, Division of Rheumatology, and Cancer Biology and Epigenomics Program, and Department of Orthopedic Surgery, and Department of Pediatric Neurosurgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois; Cure Juvenile Myositis (JM) Program of Excellence in JM Research and Care, Encinitas, California; Joseph J. Zilber School of Public Health, University of Wisconsin, Milwaukee, Wisconsin, USA.D. Xu, MD, Research Assistant Professor, Stanley Manne Children's Research Institute, and Cure JM Program of Excellence in JM Research and Care, and Department of Pediatrics, Division of Rheumatology, Northwestern University Feinberg School of Medicine; C.C. Huang, PhD, Associate Professor, Joseph J. Zilber School of Public Health, University of Wisconsin; A. Kachaochana, BS, Laboratory Technician 2, Stanley Manne Children's Research Institute, and Cure JM Program of Excellence in JM Research and Care; G.A. Morgan, MA, Database Manager, Stanley Manne Children's Research Institute, and Cure JM Program of Excellence in JM Research and Care; M. Bonaldo, Ph.D., Research Associate Professor, Stanley Manne Children's Research Institute, and Cancer Biology and Epigenomics Program, Northwestern University Feinberg School of Medicine; M.B. Soares, PhD, Rachelle and Mark Gordon Endowed Professorship in Cancer Biology and Epigenomics, Professor of Pediatrics, Stanley Manne Children's Research Institute, and Cancer Biology and Epigenomics Program, Northwestern University Feinberg School of Medicine; F. Costa, PhD, Associate Professor of Pediatrics, Stanley Manne Children's Research Institute, and Cancer Biology and Epigenomics Program, Northwestern University Feinberg School of Medicine; J.F. Sarwark, MD, Professor of Orthopedic Surgery, Department of Orthopedic Surgery, Northwestern University Feinberg School of Medicine; S.T. Sredni, MD,
authors.forename: Dong
authors.initials: D
authors.lastname: Xu
authors.affiliation: From the Stanley Manne Children's Research Institute; Ann and Robert H. Lurie Children's Hospital of Chicago; Department of Pediatrics, Division of Rheumatology, and Cancer Biology and Epigenomics Program, and Department of Orthopedic Surgery, and Department of Pediatric Neurosurgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois; Cure Juvenile Myositis (JM) Program of Excellence in JM Research and Care, Encinitas, California; Joseph J. Zilber School of Public Health, University of Wisconsin, Milwaukee, Wisconsin, USA.D. Xu, MD, Research Assistant Professor, Stanley Manne Children's Research Institute, and Cure JM Program of Excellence in JM Research and Care, and Department of Pediatrics, Division of Rheumatology, Northwestern University Feinberg School of Medicine; C.C. Huang, PhD, Associate Professor, Joseph J. Zilber School of Public Health, University of Wisconsin; A. Kachaochana, BS, Laboratory Technician 2, Stanley Manne Children's Research Institute, and Cure JM Program of Excellence in JM Research and Care; G.A. Morgan, MA, Database Manager, Stanley Manne Children's Research Institute, and Cure JM Program of Excellence in JM Research and Care; M. Bonaldo, Ph.D., Research Associate Professor, Stanley Manne Children's Research Institute, and Cancer Biology and Epigenomics Program, Northwestern University Feinberg School of Medicine; M.B. Soares, PhD, Rachelle and Mark Gordon Endowed Professorship in Cancer Biology and Epigenomics, Professor of Pediatrics, Stanley Manne Children's Research Institute, and Cancer Biology and Epigenomics Program, Northwestern University Feinberg School of Medicine; F. Costa, PhD, Associate Professor of Pediatrics, Stanley Manne Children's Research Institute, and Cancer Biology and Epigenomics Program, Northwestern University Feinberg School of Medicine; J.F. Sarwark, MD, Professor of Orthopedic Surgery, Department of Orthopedic Surgery, Northwestern University Feinberg School of Medicine; S.T. Sredni, MD,
authors.forename: Chiang-Ching
authors.initials: CC
authors.lastname: Huang
authors.affiliation: From the Stanley Manne Children's Research Institute; Ann and Robert H. Lurie Children's Hospital of Chicago; Department of Pediatrics, Division of Rheumatology, and Cancer Biology and Epigenomics Program, and Department of Orthopedic Surgery, and Department of Pediatric Neurosurgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois; Cure Juvenile Myositis (JM) Program of Excellence in JM Research and Care, Encinitas, California; Joseph J. Zilber School of Public Health, University of Wisconsin, Milwaukee, Wisconsin, USA.D. Xu, MD, Research Assistant Professor, Stanley Manne Children's Research Institute, and Cure JM Program of Excellence in JM Research and Care, and Department of Pediatrics, Division of Rheumatology, Northwestern University Feinberg School of Medicine; C.C. Huang, PhD, Associate Professor, Joseph J. Zilber School of Public Health, University of Wisconsin; A. Kachaochana, BS, Laboratory Technician 2, Stanley Manne Children's Research Institute, and Cure JM Program of Excellence in JM Research and Care; G.A. Morgan, MA, Database Manager, Stanley Manne Children's Research Institute, and Cure JM Program of Excellence in JM Research and Care; M. Bonaldo, Ph.D., Research Associate Professor, Stanley Manne Children's Research Institute, and Cancer Biology and Epigenomics Program, Northwestern University Feinberg School of Medicine; M.B. Soares, PhD, Rachelle and Mark Gordon Endowed Professorship in Cancer Biology and Epigenomics, Professor of Pediatrics, Stanley Manne Children's Research Institute, and Cancer Biology and Epigenomics Program, Northwestern University Feinberg School of Medicine; F. Costa, PhD, Associate Professor of Pediatrics, Stanley Manne Children's Research Institute, and Cancer Biology and Epigenomics Program, Northwestern University Feinberg School of Medicine; J.F. Sarwark, MD, Professor of Orthopedic Surgery, Department of Orthopedic Surgery, Northwestern University Feinberg School of Medicine; S.T. Sredni, MD,
authors.forename: Akadia
authors.initials: A
authors.lastname: Kachaochana
authors.affiliation: From the Stanley Manne Children's Research Institute; Ann and Robert H. Lurie Children's Hospital of Chicago; Department of Pediatrics, Division of Rheumatology, and Cancer Biology and Epigenomics Program, and Department of Orthopedic Surgery, and Department of Pediatric Neurosurgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois; Cure Juvenile Myositis (JM) Program of Excellence in JM Research and Care, Encinitas, California; Joseph J. Zilber School of Public Health, University of Wisconsin, Milwaukee, Wisconsin, USA.D. Xu, MD, Research Assistant Professor, Stanley Manne Children's Research Institute, and Cure JM Program of Excellence in JM Research and Care, and Department of Pediatrics, Division of Rheumatology, Northwestern University Feinberg School of Medicine; C.C. Huang, PhD, Associate Professor, Joseph J. Zilber School of Public Health, University of Wisconsin; A. Kachaochana, BS, Laboratory Technician 2, Stanley Manne Children's Research Institute, and Cure JM Program of Excellence in JM Research and Care; G.A. Morgan, MA, Database Manager, Stanley Manne Children's Research Institute, and Cure JM Program of Excellence in JM Research and Care; M. Bonaldo, Ph.D., Research Associate Professor, Stanley Manne Children's Research Institute, and Cancer Biology and Epigenomics Program, Northwestern University Feinberg School of Medicine; M.B. Soares, PhD, Rachelle and Mark Gordon Endowed Professorship in Cancer Biology and Epigenomics, Professor of Pediatrics, Stanley Manne Children's Research Institute, and Cancer Biology and Epigenomics Program, Northwestern University Feinberg School of Medicine; F. Costa, PhD, Associate Professor of Pediatrics, Stanley Manne Children's Research Institute, and Cancer Biology and Epigenomics Program, Northwestern University Feinberg School of Medicine; J.F. Sarwark, MD, Professor of Orthopedic Surgery, Department of Orthopedic Surgery, Northwestern University Feinberg School of Medicine; S.T. Sredni, MD,
authors.forename: Gabrielle A
authors.initials: GA
authors.lastname: Morgan
authors.affiliation: From the Stanley Manne Children's Research Institute; Ann and Robert H. Lurie Children's Hospital of Chicago; Department of Pediatrics, Division of Rheumatology, and Cancer Biology and Epigenomics Program, and Department of Orthopedic Surgery, and Department of Pediatric Neurosurgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois; Cure Juvenile Myositis (JM) Program of Excellence in JM Research and Care, Encinitas, California; Joseph J. Zilber School of Public Health, University of Wisconsin, Milwaukee, Wisconsin, USA.D. Xu, MD, Research Assistant Professor, Stanley Manne Children's Research Institute, and Cure JM Program of Excellence in JM Research and Care, and Department of Pediatrics, Division of Rheumatology, Northwestern University Feinberg School of Medicine; C.C. Huang, PhD, Associate Professor, Joseph J. Zilber School of Public Health, University of Wisconsin; A. Kachaochana, BS, Laboratory Technician 2, Stanley Manne Children's Research Institute, and Cure JM Program of Excellence in JM Research and Care; G.A. Morgan, MA, Database Manager, Stanley Manne Children's Research Institute, and Cure JM Program of Excellence in JM Research and Care; M. Bonaldo, Ph.D., Research Associate Professor, Stanley Manne Children's Research Institute, and Cancer Biology and Epigenomics Program, Northwestern University Feinberg School of Medicine; M.B. Soares, PhD, Rachelle and Mark Gordon Endowed Professorship in Cancer Biology and Epigenomics, Professor of Pediatrics, Stanley Manne Children's Research Institute, and Cancer Biology and Epigenomics Program, Northwestern University Feinberg School of Medicine; F. Costa, PhD, Associate Professor of Pediatrics, Stanley Manne Children's Research Institute, and Cancer Biology and Epigenomics Program, Northwestern University Feinberg School of Medicine; J.F. Sarwark, MD, Professor of Orthopedic Surgery, Department of Orthopedic Surgery, Northwestern University Feinberg School of Medicine; S.T. Sredni, MD,
authors.forename: Maria F
authors.initials: MF
authors.lastname: Bonaldo
authors.affiliation: From the Stanley Manne Children's Research Institute; Ann and Robert H. Lurie Children's Hospital of Chicago; Department of Pediatrics, Division of Rheumatology, and Cancer Biology and Epigenomics Program, and Department of Orthopedic Surgery, and Department of Pediatric Neurosurgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois; Cure Juvenile Myositis (JM) Program of Excellence in JM Research and Care, Encinitas, California; Joseph J. Zilber School of Public Health, University of Wisconsin, Milwaukee, Wisconsin, USA.D. Xu, MD, Research Assistant Professor, Stanley Manne Children's Research Institute, and Cure JM Program of Excellence in JM Research and Care, and Department of Pediatrics, Division of Rheumatology, Northwestern University Feinberg School of Medicine; C.C. Huang, PhD, Associate Professor, Joseph J. Zilber School of Public Health, University of Wisconsin; A. Kachaochana, BS, Laboratory Technician 2, Stanley Manne Children's Research Institute, and Cure JM Program of Excellence in JM Research and Care; G.A. Morgan, MA, Database Manager, Stanley Manne Children's Research Institute, and Cure JM Program of Excellence in JM Research and Care; M. Bonaldo, Ph.D., Research Associate Professor, Stanley Manne Children's Research Institute, and Cancer Biology and Epigenomics Program, Northwestern University Feinberg School of Medicine; M.B. Soares, PhD, Rachelle and Mark Gordon Endowed Professorship in Cancer Biology and Epigenomics, Professor of Pediatrics, Stanley Manne Children's Research Institute, and Cancer Biology and Epigenomics Program, Northwestern University Feinberg School of Medicine; F. Costa, PhD, Associate Professor of Pediatrics, Stanley Manne Children's Research Institute, and Cancer Biology and Epigenomics Program, Northwestern University Feinberg School of Medicine; J.F. Sarwark, MD, Professor of Orthopedic Surgery, Department of Orthopedic Surgery, Northwestern University Feinberg School of Medicine; S.T. Sredni, MD,
authors.forename: Marcelo B
authors.initials: MB
authors.lastname: Soares
authors.affiliation: From the Stanley Manne Children's Research Institute; Ann and Robert H. Lurie Children's Hospital of Chicago; Department of Pediatrics, Division of Rheumatology, and Cancer Biology and Epigenomics Program, and Department of Orthopedic Surgery, and Department of Pediatric Neurosurgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois; Cure Juvenile Myositis (JM) Program of Excellence in JM Research and Care, Encinitas, California; Joseph J. Zilber School of Public Health, University of Wisconsin, Milwaukee, Wisconsin, USA.D. Xu, MD, Research Assistant Professor, Stanley Manne Children's Research Institute, and Cure JM Program of Excellence in JM Research and Care, and Department of Pediatrics, Division of Rheumatology, Northwestern University Feinberg School of Medicine; C.C. Huang, PhD, Associate Professor, Joseph J. Zilber School of Public Health, University of Wisconsin; A. Kachaochana, BS, Laboratory Technician 2, Stanley Manne Children's Research Institute, and Cure JM Program of Excellence in JM Research and Care; G.A. Morgan, MA, Database Manager, Stanley Manne Children's Research Institute, and Cure JM Program of Excellence in JM Research and Care; M. Bonaldo, Ph.D., Research Associate Professor, Stanley Manne Children's Research Institute, and Cancer Biology and Epigenomics Program, Northwestern University Feinberg School of Medicine; M.B. Soares, PhD, Rachelle and Mark Gordon Endowed Professorship in Cancer Biology and Epigenomics, Professor of Pediatrics, Stanley Manne Children's Research Institute, and Cancer Biology and Epigenomics Program, Northwestern University Feinberg School of Medicine; F. Costa, PhD, Associate Professor of Pediatrics, Stanley Manne Children's Research Institute, and Cancer Biology and Epigenomics Program, Northwestern University Feinberg School of Medicine; J.F. Sarwark, MD, Professor of Orthopedic Surgery, Department of Orthopedic Surgery, Northwestern University Feinberg School of Medicine; S.T. Sredni, MD,
authors.forename: Fabricio
authors.initials: F
authors.lastname: Costa
authors.affiliation: From the Stanley Manne Children's Research Institute; Ann and Robert H. Lurie Children's Hospital of Chicago; Department of Pediatrics, Division of Rheumatology, and Cancer Biology and Epigenomics Program, and Department of Orthopedic Surgery, and Department of Pediatric Neurosurgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois; Cure Juvenile Myositis (JM) Program of Excellence in JM Research and Care, Encinitas, California; Joseph J. Zilber School of Public Health, University of Wisconsin, Milwaukee, Wisconsin, USA.D. Xu, MD, Research Assistant Professor, Stanley Manne Children's Research Institute, and Cure JM Program of Excellence in JM Research and Care, and Department of Pediatrics, Division of Rheumatology, Northwestern University Feinberg School of Medicine; C.C. Huang, PhD, Associate Professor, Joseph J. Zilber School of Public Health, University of Wisconsin; A. Kachaochana, BS, Laboratory Technician 2, Stanley Manne Children's Research Institute, and Cure JM Program of Excellence in JM Research and Care; G.A. Morgan, MA, Database Manager, Stanley Manne Children's Research Institute, and Cure JM Program of Excellence in JM Research and Care; M. Bonaldo, Ph.D., Research Associate Professor, Stanley Manne Children's Research Institute, and Cancer Biology and Epigenomics Program, Northwestern University Feinberg School of Medicine; M.B. Soares, PhD, Rachelle and Mark Gordon Endowed Professorship in Cancer Biology and Epigenomics, Professor of Pediatrics, Stanley Manne Children's Research Institute, and Cancer Biology and Epigenomics Program, Northwestern University Feinberg School of Medicine; F. Costa, PhD, Associate Professor of Pediatrics, Stanley Manne Children's Research Institute, and Cancer Biology and Epigenomics Program, Northwestern University Feinberg School of Medicine; J.F. Sarwark, MD, Professor of Orthopedic Surgery, Department of Orthopedic Surgery, Northwestern University Feinberg School of Medicine; S.T. Sredni, MD,
authors.forename: John
authors.initials: J
authors.lastname: Sarwark
authors.affiliation: From the Stanley Manne Children's Research Institute; Ann and Robert H. Lurie Children's Hospital of Chicago; Department of Pediatrics, Division of Rheumatology, and Cancer Biology and Epigenomics Program, and Department of Orthopedic Surgery, and Department of Pediatric Neurosurgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois; Cure Juvenile Myositis (JM) Program of Excellence in JM Research and Care, Encinitas, California; Joseph J. Zilber School of Public Health, University of Wisconsin, Milwaukee, Wisconsin, USA.D. Xu, MD, Research Assistant Professor, Stanley Manne Children's Research Institute, and Cure JM Program of Excellence in JM Research and Care, and Department of Pediatrics, Division of Rheumatology, Northwestern University Feinberg School of Medicine; C.C. Huang, PhD, Associate Professor, Joseph J. Zilber School of Public Health, University of Wisconsin; A. Kachaochana, BS, Laboratory Technician 2, Stanley Manne Children's Research Institute, and Cure JM Program of Excellence in JM Research and Care; G.A. Morgan, MA, Database Manager, Stanley Manne Children's Research Institute, and Cure JM Program of Excellence in JM Research and Care; M. Bonaldo, Ph.D., Research Associate Professor, Stanley Manne Children's Research Institute, and Cancer Biology and Epigenomics Program, Northwestern University Feinberg School of Medicine; M.B. Soares, PhD, Rachelle and Mark Gordon Endowed Professorship in Cancer Biology and Epigenomics, Professor of Pediatrics, Stanley Manne Children's Research Institute, and Cancer Biology and Epigenomics Program, Northwestern University Feinberg School of Medicine; F. Costa, PhD, Associate Professor of Pediatrics, Stanley Manne Children's Research Institute, and Cancer Biology and Epigenomics Program, Northwestern University Feinberg School of Medicine; J.F. Sarwark, MD, Professor of Orthopedic Surgery, Department of Orthopedic Surgery, Northwestern University Feinberg School of Medicine; S.T. Sredni, MD,
authors.forename: Simone T
authors.initials: ST
authors.lastname: Sredni
authors.affiliation: From the Stanley Manne Children's Research Institute; Ann and Robert H. Lurie Children's Hospital of Chicago; Department of Pediatrics, Division of Rheumatology, and Cancer Biology and Epigenomics Program, and Department of Orthopedic Surgery, and Department of Pediatric Neurosurgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois; Cure Juvenile Myositis (JM) Program of Excellence in JM Research and Care, Encinitas, California; Joseph J. Zilber School of Public Health, University of Wisconsin, Milwaukee, Wisconsin, USA.D. Xu, MD, Research Assistant Professor, Stanley Manne Children's Research Institute, and Cure JM Program of Excellence in JM Research and Care, and Department of Pediatrics, Division of Rheumatology, Northwestern University Feinberg School of Medicine; C.C. Huang, PhD, Associate Professor, Joseph J. Zilber School of Public Health, University of Wisconsin; A. Kachaochana, BS, Laboratory Technician 2, Stanley Manne Children's Research Institute, and Cure JM Program of Excellence in JM Research and Care; G.A. Morgan, MA, Database Manager, Stanley Manne Children's Research Institute, and Cure JM Program of Excellence in JM Research and Care; M. Bonaldo, Ph.D., Research Associate Professor, Stanley Manne Children's Research Institute, and Cancer Biology and Epigenomics Program, Northwestern University Feinberg School of Medicine; M.B. Soares, PhD, Rachelle and Mark Gordon Endowed Professorship in Cancer Biology and Epigenomics, Professor of Pediatrics, Stanley Manne Children's Research Institute, and Cancer Biology and Epigenomics Program, Northwestern University Feinberg School of Medicine; F. Costa, PhD, Associate Professor of Pediatrics, Stanley Manne Children's Research Institute, and Cancer Biology and Epigenomics Program, Northwestern University Feinberg School of Medicine; J.F. Sarwark, MD, Professor of Orthopedic Surgery, Department of Orthopedic Surgery, Northwestern University Feinberg School of Medicine; S.T. Sredni, MD,
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Pachman
mesh_terms: D001707:Biopsy, Needle; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000378:metabolism; D003882:Dermatomyositis / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D061705:Image-Guided Biopsy; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D012016:Reference Values; D012494:Sampling Studies; D012720:Severity of Illness Index
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D035683:MicroRNAs
keywords: INFLAMMATORY CYTOKINES; JUVENILE DERMATOMYOSITIS; MicroRNA MICROARRAY; MicroRNA-10