| |  Online-Ressource |
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| Verfasst von: | Pellegrino, Rossella [VerfasserIn]  |
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| | Thavamani, Abhishek [VerfasserIn] |
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| | Calvisi, Diego F. [VerfasserIn] |
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| | Budczies, Jan [VerfasserIn] |
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| | Neumann, Ariane [VerfasserIn] |
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| | Geffers, Robert [VerfasserIn] |
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| | Krömer, Jasmin [VerfasserIn] |
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| | Greule, Damaris [VerfasserIn] |
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| | Schirmacher, Peter [VerfasserIn] |
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| | Nordheim, Alfred [VerfasserIn] |
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| | Longerich, Thomas [VerfasserIn] |
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| Titel: | Serum Response Factor (SRF) drives the transcriptional upregulation of the MDM4 oncogene in HCC |
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| Verf.angabe: | Rossella Pellegrino, Abhishek Thavamani, Diego F. Calvisi, Jan Budczies, Ariane Neumann, Robert Geffers, Jasmin Kroemer, Damaris Greule, Peter Schirmacher, Alfred Nordheim and Thomas Longerich |
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| E-Jahr: | 2021 |
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| Jahr: | 8 January 2021 |
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| Teil: | volume:13 |
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| | year:2021 |
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| | number:2 |
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| Fussnoten: | Gesehen am 02.03.2021 |
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| Titel Quelle: | Enthalten in: Cancers |
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| Ort Quelle: | Basel : MDPI, 2009 |
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| Jahr Quelle: | 2021 |
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| Band/Heft Quelle: | 13(2021,2) Artikel-Nummer 199, 17 Seiten |
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| ISSN Quelle: | 2072-6694 |
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| Abstract: | Different molecular mechanisms support the overexpression of the mouse double minute homolog 4 (MDM4), a functional p53 inhibitor, in human hepatocellular carcinoma (HCC). However, the transcription factors (TFs) leading to its transcriptional upregulation remain unknown. Following promoter and gene expression analyses, putative TFs were investigated using gene-specific siRNAs, cDNAs, luciferase reporter assays, chromatin immunoprecipitation, and XI-011 drug treatment in vitro. Additionally, MDM4 expression was investigated in SRF-VP16iHep transgenic mice. We observed a copy-number-independent upregulation of MDM4 in human HCCs. Serum response factor (SRF), ELK1 and ELK4 were identified as TFs activating MDM4 transcription. While SRF was constitutively detected in TF complexes at the MDM4 promoter, presence of ELK1 and ELK4 was cell-type dependent. Furthermore, MDM4 was upregulated in SRF-VP16-driven murine liver tumors. The pharmacological inhibitor XI-011 exhibited anti-MDM4 activity by downregulating the TFs driving MDM4 transcription, which decreased HCC cell viability and increased apoptosis. In conclusion, SRF drives transcriptional MDM4 upregulation in HCC, acting in concert with either ELK1 or ELK4. The transcriptional regulation of MDM4 may be a promising target for precision oncology of human HCC, as XI-011 treatment exerts anti-MDM4 activity independent from the MDM4 copy number and the p53 status. |
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| DOI: | doi:10.3390/cancers13020199 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext ; Verlag: https://doi.org/10.3390/cancers13020199 |
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| | Volltext: https://www.mdpi.com/2072-6694/13/2/199 |
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| | DOI: https://doi.org/10.3390/cancers13020199 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | <i>MDM4</i> transcriptional regulation |
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| | ELK1 |
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| | ELK4 |
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| | ERK |
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| | ETS transcription factors |
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| | HCC |
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| | MDM4 |
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| | SRF |
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| | tumor protein p53 |
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| | XI-011 |
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| K10plus-PPN: | 1750175533 |
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| Verknüpfungen: | → Zeitschrift |
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Serum Response Factor (SRF) drives the transcriptional upregulation of the MDM4 oncogene in HCC / Pellegrino, Rossella [VerfasserIn]; 8 January 2021 (Online-Ressource)
