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@ARTICLE{Fellenberg:125811,
      author       = {J. Fellenberg and H. Sähr and P. Kunz and Z. Zhao and L.
                      Liu and D. Tichy$^*$ and I. Herr},
      title        = {{R}estoration of mi{R}-127-3p and mi{R}-376a-3p counteracts
                      the neoplastic phenotype of giant cell tumor of bone derived
                      stromal cells by targeting {COA}1, {GLE}1 and {PDIA}6.},
      journal      = {Cancer letters},
      volume       = {371},
      number       = {1},
      issn         = {0304-3835},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier Science},
      reportid     = {DKFZ-2017-01935},
      pages        = {134 - 141},
      year         = {2016},
      abstract     = {Although generally benign, giant cell tumors of bone (GCTB)
                      display an aggressive behavior associated with significant
                      bone destruction and lung metastasis in rare cases. This and
                      the very high recurrence rate observed after surgical
                      resection ranging from 20 to $55\%$ necessitates the
                      development of more effective treatment strategies. To
                      identify valuable therapeutic targets, we screened a
                      previously identified microRNA signature consisting of 23
                      microRNAs predominantly down-regulated in GCTB. We
                      preselected eight candidate microRNAs and analyzed the
                      impact of their restored expression on the neoplastic
                      phenotype of GCTB stromal cells (GCTSC). A consistent and
                      significant inhibition of cell proliferation, migration,
                      colony formation and spheroid formation could be induced by
                      transfection of primary GCTSC cell lines with miR-127-3p and
                      miR-376a-3p, respectively. Genome wide expression analysis
                      of miR-127-3p and miR-376a-3p transfected cells revealed
                      four novel target genes for each microRNA. Luciferase
                      reporter assays demonstrated direct interactions of
                      miR-127-3p with COA1 and direct interaction of miR-376a-3p
                      with GLE1 and PDIA6, suggesting a pivotal role of these
                      genes in the molecular etiology of GTCB. Interestingly, both
                      microRNAs are located within a chromosomal region frequently
                      silenced in GCTB and many other types of cancers, indicating
                      that these microRNAs and their target genes are valuable
                      therapeutic targets for the treatment of GCTB and possibly
                      other tumor entities.},
      keywords     = {Gle1 protein, human (NLM Chemicals) / MIRN127 microRNA,
                      human (NLM Chemicals) / MIRN376 microRNA, human (NLM
                      Chemicals) / MicroRNAs (NLM Chemicals) / Nucleocytoplasmic
                      Transport Proteins (NLM Chemicals) / PDIA6 protein, human
                      (NLM Chemicals) / Protein Disulfide-Isomerases (NLM
                      Chemicals)},
      cin          = {C060},
      ddc          = {570},
      cid          = {I:(DE-He78)C060-20160331},
      pnm          = {313 - Cancer risk factors and prevention (POF3-313)},
      pid          = {G:(DE-HGF)POF3-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:26655997},
      doi          = {10.1016/j.canlet.2015.10.039},
      url          = {https://inrepo02.dkfz.de/record/125811},
}