% 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{Krebs:287641,
      author       = {M. Krebs and M. J. Kotlyar and J. Fahl and S. Janaki Raman
                      and F. Röhrig and A. Marquardt and H. Kübler and B. Kneitz
                      and A. Schulze$^*$ and C. Kalogirou},
      title        = {{M}etformin {R}egulates the mi{R}-205/{VEGFA} {A}xis in
                      {R}enal {C}ell {C}arcinoma {C}ells: {E}xploring a {C}linical
                      {S}ynergism with {T}yrosine {K}inase {I}nhibitors.},
      journal      = {Urologia internationalis},
      volume       = {108},
      number       = {1},
      issn         = {0042-1138},
      address      = {Basel},
      publisher    = {Karger},
      reportid     = {DKFZ-2024-00285},
      pages        = {49 - 59},
      year         = {2024},
      abstract     = {Metformin (MF) intake could be associated with a favorable
                      outcome in sunitinib (SUT)- and axitinib (AX)-treated clear
                      cell renal cell carcinoma (ccRCC) patients. Functionally, MF
                      induces miR-205, a microRNA serving as a tumor suppressor in
                      several cancers.Real-time quantitative PCR, viability
                      assays, and Western blotting analyzed MF and SUT/AX effects
                      in RCC4 and 786-O cells. A tetracycline-inducible
                      overexpression model was used to study the role of miR-205
                      and its known target gene, VEGFA. We analyzed miR-205 and
                      VEGFA within a public and an in-house ccRCC cohort. Human
                      umbilical vein endothelial cell (HUVEC) sprouting assays
                      examined miR-205 effects on angiogenesis initiation. To
                      determine the influence of the von Hippel-Lindau tumor
                      suppressor (VHL), we examined VHLwt reexpressing RCC4 and
                      786-O cells.Viability assays confirmed a sensitizing effect
                      of MF toward SUT/AX in RCC4 and 786-O cells. Overexpression
                      of miR-205 diminished VEGFA expression - as did treatment
                      with MF. Tumor tissue displayed a downregulation of miR-205
                      and an upregulation of VEGFA. Accordingly, miR-205 caused
                      less and shorter vessel sprouts in HUVEC assays. Finally,
                      VHLwt-expressing RCC4 and 786-O cells displayed higher
                      miR-205 and lower VEGFA levels.Our results support the
                      protective role of MF in ccRCC and offer functional insights
                      into the clinical synergism with tyrosine kinase
                      inhibitors.},
      keywords     = {Humans / Carcinoma, Renal Cell: drug therapy / Carcinoma,
                      Renal Cell: genetics / Carcinoma, Renal Cell: pathology /
                      Kidney Neoplasms: drug therapy / Kidney Neoplasms: genetics
                      / Kidney Neoplasms: pathology / Tyrosine Kinase Inhibitors /
                      Metformin: pharmacology / Cell Line, Tumor / MicroRNAs:
                      genetics / Sunitinib: pharmacology / Gene Expression
                      Regulation, Neoplastic / Cell Proliferation: genetics /
                      Vascular Endothelial Growth Factor A: metabolism /
                      Angiogenesis (Other) / Kidney cancer (Other) / Metformin
                      (Other) / MicroRNA (Other) / Tyrosine kinase inhibitor
                      (Other) / Tyrosine Kinase Inhibitors (NLM Chemicals) /
                      Metformin (NLM Chemicals) / MicroRNAs (NLM Chemicals) /
                      Sunitinib (NLM Chemicals) / VEGFA protein, human (NLM
                      Chemicals) / Vascular Endothelial Growth Factor A (NLM
                      Chemicals) / MIRN205 microRNA, human (NLM Chemicals)},
      cin          = {A410},
      ddc          = {610},
      cid          = {I:(DE-He78)A410-20160331},
      pnm          = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
      pid          = {G:(DE-HGF)POF4-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:38035560},
      pmc          = {pmc:PMC10836959},
      doi          = {10.1159/000535025},
      url          = {https://inrepo02.dkfz.de/record/287641},
}