% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{FahimGolestaneh:141806,
      author       = {A. Fahim Golestaneh$^*$ and L. S. M. Lecker$^*$ and J.
                      Schlegel$^*$ and A. Nowrouzi$^*$ and C. Schwager$^*$ and S.
                      Meister$^*$ and W. Weichert$^*$ and J. Debus$^*$ and A.
                      Abdollahi$^*$},
      title        = {{L}arge scale in-vivo micro-{RNA} loss of function screen
                      identified mi{R}-29a, mi{R}-100 and mi{R}-155 as modulators
                      of radioresistance and tumor-stroma communication.},
      journal      = {International journal of cancer},
      volume       = {144},
      number       = {11},
      issn         = {0020-7136},
      address      = {Bognor Regis},
      publisher    = {Wiley-Liss},
      reportid     = {DKFZ-2018-02074},
      pages        = {2774-2781},
      year         = {2019},
      abstract     = {Micro RNAs (miR) are master regulators of cellular
                      transcriptome. We aimed to investigate the role of miR
                      regulation on tumor radiosensitivity and development of
                      local tumor recurrence by a novel large-scale in-vivo loss
                      of function screen. For stable miR silencing, human A431
                      tumor cells were transduced with lentiviral constructs
                      against 170 validated human miR (miRzip library).
                      Fractionated radiotherapy (5x6Gy) was applied to A431 miRzip
                      library growing s.c. in NCr nude mice. Enrichment of miRZip
                      and miR expression was assessed using multiplexed qRT-PCR.
                      The modulatory effect of miR on tumor and tumor
                      microenvironment response to ionizing radiation was further
                      evaluated by clonogenic survival, apoptosis (Caspase 3/7),
                      DNA double-strand breaks (DSB, nuclear γH2AX foci), tumor
                      microvessel density (MVD), transcriptome and protein
                      analysis. Fractionated irradiation of the A431 miRzip
                      library led to regression of tumors. However, after a
                      latency period, tumors ultimately progressed and formed
                      local recurrences indicating the survival of a subpopulation
                      of miRzip expressing tumor clones. Among the selected miR
                      for subsequent validation studies, loss of miR-29a, miR-100
                      and miR-155 was found to enhance clonogenic survival, reduce
                      apoptosis and residual γH2AX foci of irradiated tumor
                      cells. Moreover, knockdown of miR increased tumor
                      angiogenesis correlating with elevated VEGF and TGFα
                      expression levels. This phenomenon was most evident after
                      tumor irradiation in-vivo suggesting a critical role for
                      tumor-stroma communication in development of the
                      radioresistant phenotype. Engineering radioresistant tumors
                      in-vivo by modulating miR expression may lead to
                      identification of critical targets for conquering local
                      therapy failure. This article is protected by copyright. All
                      rights reserved.},
      cin          = {E210 / E050 / L101},
      ddc          = {610},
      cid          = {I:(DE-He78)E210-20160331 / I:(DE-He78)E050-20160331 /
                      I:(DE-He78)L101-20160331},
      pnm          = {315 - Imaging and radiooncology (POF3-315)},
      pid          = {G:(DE-HGF)POF3-315},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:30478850},
      doi          = {10.1002/ijc.32019},
      url          = {https://inrepo02.dkfz.de/record/141806},
}