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@ARTICLE{Goeppert:143225,
      author       = {B. Goeppert and F. Truckenmueller and A. Ori and V. Fritz
                      and T. Albrecht and A. Fraas and D. Scherer and R. G. Silos
                      and C. Sticht and N. Gretz and A. Mehrabi and M.
                      Bewerunge-Hudler$^*$ and S. Pusch$^*$ and J. L. Bermejo and
                      P. Dietrich and P. Schirmacher and M. Renner and S.
                      Roessler},
      title        = {{P}rofiling of gallbladder carcinoma reveals distinct
                      mi{RNA} profiles and activation of {STAT}1 by the tumor
                      suppressive mi{RNA}-145-5p.},
      journal      = {Scientific reports},
      volume       = {9},
      number       = {1},
      issn         = {2045-2322},
      address      = {[London]},
      publisher    = {Macmillan Publishers Limited, part of Springer Nature},
      reportid     = {DKFZ-2019-00824},
      pages        = {4796},
      year         = {2019},
      abstract     = {Gallbladder carcinoma (GBC) is a biliary tract cancer with
                      few treatment options and poor prognosis. Radical surgery is
                      the only potentially curative treatment option but most
                      patients diagnosed with GBC are unresectable. Thus, there is
                      a great need for the development of new treatment options
                      including targeted therapy. Here, we aimed at identifying
                      deregulated miRNAs and affected pathways involved in GBC
                      development and progression. We performed global miRNA
                      profiling of 40 GBC and 8 normal gallbladder tissues and
                      identified large differences with $30\%$ of miRNAs being
                      differentially expressed (false discovery
                      rate: FDR < 0.001). We found 24 miRNAs to be
                      differentially regulated in GBC with poor outcome
                      (p < 0.05) of which miR-145-5p was the most
                      downregulated miRNA. Overexpression of miR-145-5p
                      significantly reduced cell proliferation and colony
                      formation. Gene expression analysis of cells expressing
                      miR-145-5p mimics revealed activation of the Signal
                      transducer and activator of transcription 1 (STAT1)
                      signaling pathway which is mainly tumor suppressive.
                      Furthermore, the activation of STAT1 by miR-145-5p was
                      specifically observed in gallbladder
                      carcinoma and cholangiocarcinoma but not in hepatocellular
                      carcinoma cells. The Protein Tyrosine Phosphatase Receptor
                      Type F (PTPRF) is downregulated upon miR-145 expression and
                      may be involved in STAT1 regulation. In addition, we found
                      that the STAT1-regulated protein IRF7 is downregulated in
                      GBC compared to normal gallbladder tissue and low IRF7
                      expression is associated with significantly lower overall
                      survival of GBC patients. Thus, this study identified GBC
                      patient subgroups and provides new mechanistic insights in
                      the tumor suppressive function of miR-145-5p leading to
                      activation of STAT1 signaling.},
      cin          = {W110 / B300},
      ddc          = {600},
      cid          = {I:(DE-He78)W110-20160331 / I:(DE-He78)B300-20160331},
      pnm          = {312 - Functional and structural genomics (POF3-312)},
      pid          = {G:(DE-HGF)POF3-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:30886199},
      pmc          = {pmc:PMC6423323},
      doi          = {10.1038/s41598-019-40857-3},
      url          = {https://inrepo02.dkfz.de/record/143225},
}