title: MicroRNA-21 correlates with tumorigenesis in malignant peripheral nerve sheath tumor (MPNST) via programmed cell death protein 4 (PDCD4).
abstract: OBJECTIVE
  We investigated the miRNA profile in peripheral nerve tumors and clarified the involvement of miRNA in the development and progression of MPNST in comparison with neurofibroma (NF). In addition, we attempted to seek associations between the miRNA and their potential targets in MPNST.
  
  
  METHODS
  Global miRNA expression profiling was investigated for clinical samples of 6 MPNSTs and 6 NFs. As detected by profiling analysis, the expressions of miR-21 in clinical samples of 12 MPNSTs, 11 NFs, and 5 normal nerves, and 3 MPNST cell lines were compared using quantitative real-time reverse transcription PCR. MPNST cell line (YST-1) was transfected with miR-21 inhibitor to study its effects on cell proliferation, caspase activity, and the expression of miR-21 targets.
  
  
  RESULTS
  Analysis of miRNA expression profiles in MPNST and NF revealed significantly altered expression levels of nine miRNAs, one of those, miR-21, and its putative target, programmed cell death protein 4 (PDCD4), were selected for further studies. miR-21 expression level in MPNST was significantly higher than that in NF (P < 0.05). In MPNST cells, transfection of miR-21 inhibitor significantly increased caspase activity (P < 0.01), significantly suppressed cell growth (P < 0.05), and upregulated protein level of PDCD4, indicating that miR-21 inhibitor could induce cell apoptosis of MPNST cells.
  
  
  CONCLUSIONS
  These results suggest that miR-21 plays an important role in MPNST tumorigenesis and progression through its target, PDCD4. MiR-21 and PDCD4 may be candidate novel therapeutic targets against the development or progression of MPNSTs.
authors.affiliation: Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Itani
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kunisada
authors.forename: Yuki
authors.initials: Y
authors.lastname: Morimoto
authors.forename: Aki
authors.initials: A
authors.lastname: Yoshida
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Sasaki
authors.forename: Sachio
authors.initials: S
authors.lastname: Ito
authors.forename: Mamoru
authors.initials: M
authors.lastname: Ouchida
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Sugihara
authors.forename: Kenji
authors.initials: K
authors.lastname: Shimizu
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Ozaki
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D016000:Cluster Analysis; D018450:Disease Progression; D020869:Gene Expression Profiling; D055785:Gene Knockdown Techniques; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D018317:Nerve Sheath Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009455:Neurofibroma / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D051017:Apoptosis Regulatory Proteins; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; C114487:PDCD4 protein, human; D016601:RNA-Binding Proteins