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| Home > Publications database > Metformin Regulates the miR-205/VEGFA Axis in Renal Cell Carcinoma Cells: Exploring a Clinical Synergism with Tyrosine Kinase Inhibitors. |
| Home > Publications database > Metformin Regulates the miR-205/VEGFA Axis in Renal Cell Carcinoma Cells: Exploring a Clinical Synergism with Tyrosine Kinase Inhibitors. |
| Journal Article | DKFZ-2024-00285 |
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2024
Karger
Basel
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Please use a persistent id in citations: doi:10.1159/000535025
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.
Keyword(s): Humans (MeSH) ; Carcinoma, Renal Cell: drug therapy (MeSH) ; Carcinoma, Renal Cell: genetics (MeSH) ; Carcinoma, Renal Cell: pathology (MeSH) ; Kidney Neoplasms: drug therapy (MeSH) ; Kidney Neoplasms: genetics (MeSH) ; Kidney Neoplasms: pathology (MeSH) ; Tyrosine Kinase Inhibitors (MeSH) ; Metformin: pharmacology (MeSH) ; Cell Line, Tumor (MeSH) ; MicroRNAs: genetics (MeSH) ; Sunitinib: pharmacology (MeSH) ; Gene Expression Regulation, Neoplastic (MeSH) ; Cell Proliferation: genetics (MeSH) ; Vascular Endothelial Growth Factor A: metabolism (MeSH) ; Angiogenesis ; Kidney cancer ; Metformin ; MicroRNA ; Tyrosine kinase inhibitor ; Tyrosine Kinase Inhibitors ; Metformin ; MicroRNAs ; Sunitinib ; VEGFA protein, human ; Vascular Endothelial Growth Factor A ; MIRN205 microRNA, human
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