Dokument: Characterization of the dehydrogenase-reductase DHRS2 and its involvement in histone deacetylase inhibition in urological malignancies
| Titel: | Characterization of the dehydrogenase-reductase DHRS2 and its involvement in histone deacetylase inhibition in urological malignancies | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=68058 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20250107-130042-6 | |||||||
| Kollektion: | Publikationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Texte » Artikel, Aufsatz | |||||||
| Medientyp: | Text | |||||||
| Autoren: | Müller, Melanie R. [Autor] Burmeister, Aaron [Autor] Skowron, Margaretha A. [Autor] Stephan, Alexa [Autor] Söhngen, Christian [Autor] Wollnitzke, Philipp [Autor] Petzsch, Patrick [Autor] Alves Avelar, Leandro Antonio [Autor] Kurz, Thomas [Autor] Köhrer, Karl [Autor] | |||||||
| Dateien: |
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| Stichwörter: | DHRS2, Renal cell carcinoma, Germ cell tumors, Urothelial cancer, Prostate cancer, Lipid metabolism, Histone deacetylase inhibitor, Energy metabolism | |||||||
| Beschreibung: | Background
Being implicated during tumor migration, invasion, clonogenicity, and proliferation, the nicotinamide adenine dinucleotide (NAD)/-phosphate (NADP)-dependent dehydrogenase/reductase member 2 (DHRS2) has been considered to be induced upon inhibition of histone deacetylases (HDACi). In this study, we evaluated the current knowledge on the underlying mechanisms of the (epi)genetic regulation of DHRS2, as well as its function during tumor progression. Methods DHRS2 expression was evaluated on mRNA- and protein-level upon treatment with HDACi by means of qRT-PCR and western blot analyses, respectively. Re-analysis of RNA-sequencing data gained insight into expression of specific DHRS2 isoforms, while re-analysis of ATAC-sequencing data shed light on the chromatin accessibility at the DHRS2 locus. Further examination of the energy and lipid metabolism of HDACi-treated urologic tumor cells was performed using liquid chromatography-mass spectrometry. Results Enhanced DHRS2 expression levels upon HDACi treatment were directly linked to an enhanced chromatin accessibility at the DHRS2 locus. Particularly the DHRS2 ENST00000250383.11 protein-coding isoform was increased upon HDACi treatment. Application of the HDACi quisinostat only mildly influenced the energy metabolism of urologic tumor cells, though, the analysis of the lipid metabolism showed diminished sphingosine levels, as well as decreased S1P levels. Also the ratios of S1P/sphingosine and S1P/ceramides were reduced in all four quisinostat-treated urologic tumor cells. Conclusions With the emphasis on urologic malignancies (testicular germ cell tumors, urothelial, prostate, and renal cell carcinoma), this study concluded that elevated DHRS2 levels are indicative of a successful HDACi treatment and, thereby offering a novel putative predictive biomarker. | |||||||
| Rechtliche Vermerke: | Originalveröffentlichung:
Müller, M., Burmeister, A., Skowron, M. A., Stephan, A., Söhngen, C., Wollnitzke, P., Petzsch, P., Alves Avelar, L. A., Kurz, T., Köhrer, K., Levkau, B., & Nettersheim, D. (2024). Characterization of the dehydrogenase-reductase DHRS2 and its involvement in histone deacetylase inhibition in urological malignancies. Experimental Cell Research, 439(1), Article 114055. https://doi.org/10.1016/j.yexcr.2024.114055 | |||||||
| Lizenz: |  Dieses Werk ist lizenziert unter einer Creative Commons Namensnennung 4.0 International Lizenz | |||||||
| Fachbereich / Einrichtung: | Medizinische Fakultät | |||||||
| Dokument erstellt am: | 07.01.2025 | |||||||
| Dateien geändert am: | 07.01.2025 |
