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000287641 1001_ $$aKrebs, Markus$$b0
000287641 245__ $$aMetformin Regulates the miR-205/VEGFA Axis in Renal Cell Carcinoma Cells: Exploring a Clinical Synergism with Tyrosine Kinase Inhibitors.
000287641 260__ $$aBasel$$bKarger$$c2024
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000287641 520__ $$aMetformin (MF) intake could be associated with a favorable outcome in sunitinib (SUT)- and axitinib (AX)-treated clear cell renal cell carcinoma (ccRCC) patients. Functionally, MF induces miR-205, a microRNA serving as a tumor suppressor in several cancers.Real-time quantitative PCR, viability assays, and Western blotting analyzed MF and SUT/AX effects in RCC4 and 786-O cells. A tetracycline-inducible overexpression model was used to study the role of miR-205 and its known target gene, VEGFA. We analyzed miR-205 and VEGFA within a public and an in-house ccRCC cohort. Human umbilical vein endothelial cell (HUVEC) sprouting assays examined miR-205 effects on angiogenesis initiation. To determine the influence of the von Hippel-Lindau tumor suppressor (VHL), we examined VHLwt reexpressing RCC4 and 786-O cells.Viability assays confirmed a sensitizing effect of MF toward SUT/AX in RCC4 and 786-O cells. Overexpression of miR-205 diminished VEGFA expression - as did treatment with MF. Tumor tissue displayed a downregulation of miR-205 and an upregulation of VEGFA. Accordingly, miR-205 caused less and shorter vessel sprouts in HUVEC assays. Finally, VHLwt-expressing RCC4 and 786-O cells displayed higher miR-205 and lower VEGFA levels.Our results support the protective role of MF in ccRCC and offer functional insights into the clinical synergism with tyrosine kinase inhibitors.
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000287641 650_7 $$2Other$$aAngiogenesis
000287641 650_7 $$2Other$$aKidney cancer
000287641 650_7 $$2Other$$aMetformin
000287641 650_7 $$2Other$$aMicroRNA
000287641 650_7 $$2Other$$aTyrosine kinase inhibitor
000287641 650_7 $$2NLM Chemicals$$aTyrosine Kinase Inhibitors
000287641 650_7 $$09100L32L2N$$2NLM Chemicals$$aMetformin
000287641 650_7 $$2NLM Chemicals$$aMicroRNAs
000287641 650_7 $$0V99T50803M$$2NLM Chemicals$$aSunitinib
000287641 650_7 $$2NLM Chemicals$$aVEGFA protein, human
000287641 650_7 $$2NLM Chemicals$$aVascular Endothelial Growth Factor A
000287641 650_7 $$2NLM Chemicals$$aMIRN205 microRNA, human
000287641 650_2 $$2MeSH$$aHumans
000287641 650_2 $$2MeSH$$aCarcinoma, Renal Cell: drug therapy
000287641 650_2 $$2MeSH$$aCarcinoma, Renal Cell: genetics
000287641 650_2 $$2MeSH$$aCarcinoma, Renal Cell: pathology
000287641 650_2 $$2MeSH$$aKidney Neoplasms: drug therapy
000287641 650_2 $$2MeSH$$aKidney Neoplasms: genetics
000287641 650_2 $$2MeSH$$aKidney Neoplasms: pathology
000287641 650_2 $$2MeSH$$aTyrosine Kinase Inhibitors
000287641 650_2 $$2MeSH$$aMetformin: pharmacology
000287641 650_2 $$2MeSH$$aCell Line, Tumor
000287641 650_2 $$2MeSH$$aMicroRNAs: genetics
000287641 650_2 $$2MeSH$$aSunitinib: pharmacology
000287641 650_2 $$2MeSH$$aGene Expression Regulation, Neoplastic
000287641 650_2 $$2MeSH$$aCell Proliferation: genetics
000287641 650_2 $$2MeSH$$aVascular Endothelial Growth Factor A: metabolism
000287641 7001_ $$aKotlyar, Mischa J$$b1
000287641 7001_ $$aFahl, Julian$$b2
000287641 7001_ $$aJanaki Raman, Sudha$$b3
000287641 7001_ $$aRöhrig, Florian$$b4
000287641 7001_ $$aMarquardt, André$$b5
000287641 7001_ $$aKübler, Hubert$$b6
000287641 7001_ $$aKneitz, Burkhard$$b7
000287641 7001_ $$0P:(DE-He78)94ae391f53fb9285e1b68f9930615af1$$aSchulze, Almut$$b8$$udkfz
000287641 7001_ $$aKalogirou, Charis$$b9
000287641 773__ $$0PERI:(DE-600)1464417-4$$a10.1159/000535025$$gVol. 108, no. 1, p. 49 - 59$$n1$$p49 - 59$$tUrologia internationalis$$v108$$x0042-1138$$y2024
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