SIAH3 is frequently epigenetically silenced in cancer and regulates mitochondrial metabolism.

Autor: Deutschmeyer VE; Institute for Genetics, Justus-Liebig-University Giessen, Giessen, Germany., Schlaudraff NA; Institute for Genetics, Justus-Liebig-University Giessen, Giessen, Germany., Walesch SK; Institute for Genetics, Justus-Liebig-University Giessen, Giessen, Germany., Moyer J; Institute for Genetics, Justus-Liebig-University Giessen, Giessen, Germany., Sokol AM; Biomolecular Mass Spectrometry, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany., Graumann J; Biomolecular Mass Spectrometry, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.; Institute of Translational Proteomics, Department of Medicine, Philipps-University, Marburg, Germany., Meissner W; Core Facility for Cellular Metabolism, Department of Medicine, Philipps-University, Marburg, Germany., Schneider M; Translational Research Unit, Thoraxklinik at Heidelberg University Hospital, Heidelberg, Germany.; University of Giessen Marburg Lung Center (UGMLC) and Translational Lung Research Center (TLRC) Heidelberg, German Center for Lung Research (DZL), Giessen, Germany., Muley T; Translational Research Unit, Thoraxklinik at Heidelberg University Hospital, Heidelberg, Germany.; University of Giessen Marburg Lung Center (UGMLC) and Translational Lung Research Center (TLRC) Heidelberg, German Center for Lung Research (DZL), Giessen, Germany., Helmbold P; Department of Dermatology, University of Heidelberg, Heidelberg, Germany., Schwinn M; Institute of Biochemistry, Medical Faculty of the University Giessen, Giessen, Germany., Richter AM; Institute for Genetics, Justus-Liebig-University Giessen, Giessen, Germany., Schmitz ML; Institute of Biochemistry, Medical Faculty of the University Giessen, Giessen, Germany., Dammann RH; Institute for Genetics, Justus-Liebig-University Giessen, Giessen, Germany.; University of Giessen Marburg Lung Center (UGMLC) and Translational Lung Research Center (TLRC) Heidelberg, German Center for Lung Research (DZL), Giessen, Germany.
Jazyk: angličtina
Zdroj: International journal of cancer [Int J Cancer] 2025 Jan 15; Vol. 156 (2), pp. 353-367. Date of Electronic Publication: 2024 Sep 30.
DOI: 10.1002/ijc.35202
Abstrakt: Of the seven in absentia homologue (SIAH) family, three members have been identified in the human genome. In contrast to the E3 ubiquitin ligase encoding SIAH1 and SIAH2, little is known on the regulation and function of SIAH3 in tumorigenesis. In this study, we reveal that SIAH3 is frequently epigenetically silenced in different cancer entities, including cutaneous melanoma, lung adenocarcinoma and head and neck cancer. Low SIAH3 levels correlate with an impaired survival of cancer patients. Additionally, induced expression of SIAH3 reduces cell proliferation and induces cell death. Functionally, SIAH3 negatively affects cellular metabolism by shifting cells form aerobic oxidative phosphorylation to glycolysis. SIAH3 is localized in the mitochondrion and interacts with proteins involved in mitochondrial ribosome biogenesis and translation. We also report that SIAH3 interacts with ubiquitin ligases, including SIAH1 or SIAH2, and is degraded by them. These results suggest that SIAH3 acts as an epigenetically controlled tumor suppressor by regulating cellular metabolism through the inhibition of oxidative phosphorylation.
(© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)
Databáze: MEDLINE
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