title: MicroRNAome profiling in benign and malignant neurofibromatosis type 1-associated nerve sheath tumors: evidences of PTEN pathway alterations in early NF1 tumorigenesis.
abstract: BACKGROUND
  Neurofibromatosis type 1 (NF1) is a common dominant tumor predisposition syndrome affecting 1 in 3,500 individuals. The hallmarks of NF1 are the development of peripheral nerve sheath tumors either benign (dermal and plexiform neurofibromas) or malignant (MPNSTs).
  
  
  RESULTS
  To comprehensively characterize the role of microRNAs in NF1 tumorigenesis, we analyzed 377 miRNAs expression in a large panel of dermal and plexiform neurofibromas, and MPNSTs. The most significantly upregulated miRNA in plexiform neurofibromas was miR-486-3p that targets the major tumor suppressor gene, PTEN. We confirmed PTEN downregulation at mRNA level. In plexiform neurofibromas, we also report aberrant expression of four miRNAs involved in the RAS-MAPK pathway (miR-370, miR-143, miR-181a, and miR-145). In MPNSTs, significant deregulated miRNAs were involved in PTEN repression (miR-301a, miR-19a, and miR-106b), RAS-MAPK pathway regulation (Let-7b, miR-195, and miR-10b), mesenchymal transition (miR-200c, let-7b, miR-135a, miR-135b, and miR-9), HOX genes expression (miR-210, miR-196b, miR-10a, miR-10b, and miR-9), and cell cycle progression (miR-195, let-7b, miR-20a, miR-210, miR-129-3p, miR-449a, and miR-106b).
  
  
  CONCLUSIONS
  We confirmed the implication of PTEN in genesis of plexiform neurofibromas and MPNSTs in NF1. Markedly deregulated miRNAs might have potential diagnostic or prognostic value and could represent novel strategies for effective pharmacological therapies of NF1 tumors.
authors.affiliation: UMR745 INSERM, Université Paris Descartes, Sorbonne Paris Cité, Faculté des Sciences Pharmaceutiques et Biologiques, 4 avenue de l'Observatoire, 75006 Paris, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Masliah-Planchon
authors.forename: Eric
authors.initials: E
authors.lastname: Pasmant
authors.forename: Armelle
authors.initials: A
authors.lastname: Luscan
authors.forename: Ingrid
authors.initials: I
authors.lastname: Laurendeau
authors.forename: Nicolas
authors.initials: N
authors.lastname: Ortonne
authors.forename: Mikael
authors.initials: M
authors.lastname: Hivelin
authors.forename: Jennifer
authors.initials: J
authors.lastname: Varin
authors.forename: Laurence
authors.initials: L
authors.lastname: Valeyrie-Allanore
authors.forename: Valérie
authors.initials: V
authors.lastname: Dumaine
authors.forename: Laurent
authors.initials: L
authors.lastname: Lantieri
authors.forename: Karen
authors.initials: K
authors.lastname: Leroy
authors.forename: Béatrice
authors.initials: B
authors.lastname: Parfait
authors.forename: Pierre
authors.initials: P
authors.lastname: Wolkenstein
authors.forename: Michel
authors.initials: M
authors.lastname: Vidaud
authors.forename: Dominique
authors.initials: D
authors.lastname: Vidaud
authors.forename: Ivan
authors.initials: I
authors.lastname: Bièche
mesh_terms: D060565:Argonaute Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D018318:Neurofibroma, Plexiform / Q000235:genetics / Q000473:pathology; D009456:Neurofibromatosis 1 / Q000235:genetics* / Q000473:pathology*; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D011506:Proteins / Q000235:genetics; D016601:RNA-Binding Proteins; D043244:Ribonuclease III / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D015398:Signal Transduction / Q000235:genetics*; D013997:Time Factors
chemical_list: C466422:AGO2 protein, human; D060565:Argonaute Proteins; C474043:DGCR8 protein, human; D035683:MicroRNAs; D011506:Proteins; D016601:RNA-Binding Proteins; C517918:DROSHA protein, human; D043244:Ribonuclease III; D051059:PTEN Phosphohydrolase