title: MicroRNA profiling of peripheral nerve sheath tumours identifies miR-29c as a tumour suppressor gene involved in tumour progression.
abstract: BACKGROUND
  Neurofibromatosis type 1 is one of the most common familial diseases, the hallmark of which is the development of multiple neurofibromas. These are benign nerve sheath tumours, which can transform into malignant peripheral nerve sheath tumours (MPNST).
  
  
  METHODS
  The aim of this study was to identify differentially expressed microRNA (miRNA) in neurofibromas and MPNST obtained from patients with neurofibromatosis type 1 using microarray analysis. Differential expression was validated by reverse transcription quantitative-PCR, and functional studies were performed after transfection of miRNA oligonucleotide mimics into MPNST cells.
  
  
  RESULTS
  Sixteen miRNA were significantly differentially expressed in MPNST compared with NF, and of these fourteen were downregulated in MPNST: these included miR-30e*, miR-29c*, miR-29c, miR-340*, miR-30c, miR-139-5p, miR-195, miR-151-5p, miR-342-5p, miR-146a, miR-150, miR-223, let-7 a and let-7 g with a false discovery rate of q=8.48E-03 for the least significant miRNA. In contrast, miR-210 and miR-339-5p were upregulated in MPNST compared with neurofibromas. Prediction softwares/algorithms identified a list of genes targeted by miR-29c including extracellular matrix genes and matrix metalloproteinase (MMP)-2, all of which are reported to be involved in cell migration and invasion. Functional studies in a MPNST cell line, sNF96.2, using a mimic of the mature miR-29c showed reduced invasion, whereas there was no change in proliferation. Zymography of the manipulated cells showed that MMP2 activity was also reduced when miR-29c expression was forced in sNF96.2.
  
  
  CONCLUSIONS
  We provide evidence that reduction of miR-29c has a pivotal role in the progression of nerve sheath tumours and results by increasing the invasive/migratory properties of nerve sheath tumours.
authors.affiliation: UCL Cancer Institute, 72 Huntley Street, London WC1E 6BT, UK.
authors.forename: N
authors.initials: N
authors.lastname: Presneau
authors.forename: M
authors.initials: M
authors.lastname: Eskandarpour
authors.forename: T
authors.initials: T
authors.lastname: Shemais
authors.forename: S
authors.initials: S
authors.lastname: Henderson
authors.forename: D
authors.initials: D
authors.lastname: Halai
authors.forename: R
authors.initials: R
authors.lastname: Tirabosco
authors.forename: A M
authors.initials: AM
authors.lastname: Flanagan
mesh_terms: D045744:Cell Line, Tumor; D018450:Disease Progression; D015536:Down-Regulation; D005109:Extracellular Matrix / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D016153:Genes, Suppressor; D006801:Humans; D008297:Male; D035683:MicroRNAs; D008875:Middle Aged; D018317:Nerve Sheath Neoplasms / Q000235:genetics*; D009456:Neurofibromatosis 1 / Q000235:genetics
chemical_list: C532045:MIRN29a microRNA, human; D035683:MicroRNAs