Home > Publications database > Metformin Regulates the miR-205/VEGFA Axis in Renal Cell Carcinoma Cells: Exploring a Clinical Synergism with Tyrosine Kinase Inhibitors. > print

001     287641
005     20240301121609.0
024 7 _ |a 10.1159/000535025
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024 7 _ |a 1423-0399
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037 _ _ |a DKFZ-2024-00285
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Krebs, Markus
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245 _ _ |a Metformin Regulates the miR-205/VEGFA Axis in Renal Cell Carcinoma Cells: Exploring a Clinical Synergism with Tyrosine Kinase Inhibitors.
260 _ _ |a Basel
|c 2024
|b Karger
336 7 _ |a article
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336 7 _ |a ARTICLE
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520 _ _ |a 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.
536 _ _ |a 311 - Zellbiologie und Tumorbiologie (POF4-311)
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650 _ 7 |a Angiogenesis
|2 Other
650 _ 7 |a Kidney cancer
|2 Other
650 _ 7 |a Metformin
|2 Other
650 _ 7 |a MicroRNA
|2 Other
650 _ 7 |a Tyrosine kinase inhibitor
|2 Other
650 _ 7 |a Tyrosine Kinase Inhibitors
|2 NLM Chemicals
650 _ 7 |a Metformin
|0 9100L32L2N
|2 NLM Chemicals
650 _ 7 |a MicroRNAs
|2 NLM Chemicals
650 _ 7 |a Sunitinib
|0 V99T50803M
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650 _ 7 |a VEGFA protein, human
|2 NLM Chemicals
650 _ 7 |a Vascular Endothelial Growth Factor A
|2 NLM Chemicals
650 _ 7 |a MIRN205 microRNA, human
|2 NLM Chemicals
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Carcinoma, Renal Cell: drug therapy
|2 MeSH
650 _ 2 |a Carcinoma, Renal Cell: genetics
|2 MeSH
650 _ 2 |a Carcinoma, Renal Cell: pathology
|2 MeSH
650 _ 2 |a Kidney Neoplasms: drug therapy
|2 MeSH
650 _ 2 |a Kidney Neoplasms: genetics
|2 MeSH
650 _ 2 |a Kidney Neoplasms: pathology
|2 MeSH
650 _ 2 |a Tyrosine Kinase Inhibitors
|2 MeSH
650 _ 2 |a Metformin: pharmacology
|2 MeSH
650 _ 2 |a Cell Line, Tumor
|2 MeSH
650 _ 2 |a MicroRNAs: genetics
|2 MeSH
650 _ 2 |a Sunitinib: pharmacology
|2 MeSH
650 _ 2 |a Gene Expression Regulation, Neoplastic
|2 MeSH
650 _ 2 |a Cell Proliferation: genetics
|2 MeSH
650 _ 2 |a Vascular Endothelial Growth Factor A: metabolism
|2 MeSH
700 1 _ |a Kotlyar, Mischa J
|b 1
700 1 _ |a Fahl, Julian
|b 2
700 1 _ |a Janaki Raman, Sudha
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700 1 _ |a Röhrig, Florian
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700 1 _ |a Marquardt, André
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700 1 _ |a Kübler, Hubert
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700 1 _ |a Kneitz, Burkhard
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700 1 _ |a Schulze, Almut
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700 1 _ |a Kalogirou, Charis
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773 _ _ |a 10.1159/000535025
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|t Urologia internationalis
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