title: Molecular analysis of pediatric brain tumors identifies microRNAs in pilocytic astrocytomas that target the MAPK and NF-κB pathways.
abstract: BACKGROUND
  Pilocytic astrocytomas are slow-growing tumors that usually occur in the cerebellum or in the midline along the hypothalamic/optic pathways. The most common genetic alterations in pilocytic astrocytomas activate the ERK/MAPK signal transduction pathway, which is a major driver of proliferation but is also believed to induce senescence in these tumors. Here, we have conducted a detailed investigation of microRNA and gene expression, together with pathway analysis, to improve our understanding of the regulatory mechanisms in pilocytic astrocytomas.
  
  
  RESULTS
  Pilocytic astrocytomas were found to have distinctive microRNA and gene expression profiles compared to normal brain tissue and a selection of other pediatric brain tumors. Several microRNAs found to be up-regulated in pilocytic astrocytomas are predicted to target the ERK/MAPK and NF-κB signaling pathways as well as genes involved in senescence-associated inflammation and cell cycle control. Furthermore, IGFBP7 and CEBPB, which are transcriptional inducers of the senescence-associated secretory phenotype (SASP), were also up-regulated together with the markers of senescence and inflammation, CDKN1A (p21), CDKN2A (p16) and IL1B.
  
  
  CONCLUSIONS
  These findings provide further evidence of a senescent phenotype in pilocytic astrocytomas. In addition, they suggest that the ERK/MAPK pathway, which is considered the major driver of these tumors, is regulated not only by genetic aberrations but also by microRNAs.
authors.affiliation: Centre for Genomics and Child Health, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London, E1 2AT, UK.
authors.forename: Tania A
authors.initials: TA
authors.lastname: Jones
authors.affiliation: Centre for Genomics and Child Health, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London, E1 2AT, UK.
authors.forename: Jennie N
authors.initials: JN
authors.lastname: Jeyapalan
authors.affiliation: Centre for Genomics and Child Health, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London, E1 2AT, UK.|Present address: Research Department of Pathology, Cancer Institute, University College London, 72 Huntley St, Camden Town, London, WC1E 6DD, UK.
authors.forename: Tim
authors.initials: T
authors.lastname: Forshew
authors.affiliation: Centre for Genomics and Child Health, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London, E1 2AT, UK.|Present address: Department of Neuropathology, St Jude Children's Research Hospital, Memphis, TN, 38105, USA.
authors.forename: Ruth G
authors.initials: RG
authors.lastname: Tatevossian
authors.affiliation: Centre for Genomics and Child Health, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London, E1 2AT, UK.|Present address: Inivata Limited, Li Ka Shing Centre, Cambridge, CB2 0RE, UK.
authors.forename: Andrew R J
authors.initials: AR
authors.lastname: Lawson
authors.affiliation: Centre for Genomics and Child Health, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London, E1 2AT, UK.
authors.forename: Sheena N
authors.initials: SN
authors.lastname: Patel
authors.affiliation: Centre for Genomics and Child Health, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London, E1 2AT, UK.
authors.forename: Gabriel T
authors.initials: GT
authors.lastname: Doctor
authors.affiliation: Centre for Genomics and Child Health, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London, E1 2AT, UK.
authors.forename: Muhammad A
authors.initials: MA
authors.lastname: Mumin
authors.affiliation: Department of Histopathology, Great Ormond Street Hospital for Children NHS Trust, London, WC1N 3JH, UK.|Developmental Biology and Cancer Programme, UCL-Institute of Child Health, University College London, London, WC1N 1EH, UK.
authors.forename: Simon R
authors.initials: SR
authors.lastname: Picker
authors.affiliation: Department of Neurosurgery, Great Ormond Street Hospital for Children NHS Trust, London, WC1N 3JH, UK.
authors.forename: Kim P
authors.initials: KP
authors.lastname: Phipps
authors.affiliation: Department of Oncology, Great Ormond Street Hospital for Children NHS Trust, London, WC1N 3JH, UK.
authors.forename: Antony
authors.initials: A
authors.lastname: Michalski
authors.affiliation: Department of Histopathology, Great Ormond Street Hospital for Children NHS Trust, London, WC1N 3JH, UK. t.jacques@ich.ucl.ac.uk.|Developmental Biology and Cancer Programme, UCL-Institute of Child Health, University College London, London, WC1N 1EH, UK. t.jacques@ich.ucl.ac.uk.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Jacques
authors.affiliation: Centre for Genomics and Child Health, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London, E1 2AT, UK. d.sheer@qmul.ac.uk.
authors.forename: Denise
authors.initials: D
authors.lastname: Sheer
mesh_terms: D000293:Adolescent; D001254:Astrocytoma / Q000235:genetics* / Q000378:metabolism*; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007223:Infant; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics
chemical_list: D035683:MicroRNAs; D016328:NF-kappa B; D012333:RNA, Messenger; D020929:Mitogen-Activated Protein Kinase Kinases