دورية أكاديمية
Methylglyoxal: a novel upstream regulator of DNA methylation.
| العنوان: | Methylglyoxal: a novel upstream regulator of DNA methylation. |
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| المؤلفون: | Dube G; Laboratory of Cancer Epigenetics, Faculty of Medicine, ULB-Cancer Research Center (U-CRC), Université Libre de Bruxelles (ULB), Brussels, Belgium., Tiamiou A; Metastasis Research Laboratory, GIGA-Cancer, GIGA Institute, University of Liège, Liège, Belgium., Bizet M; Laboratory of Cancer Epigenetics, Faculty of Medicine, ULB-Cancer Research Center (U-CRC), Université Libre de Bruxelles (ULB), Brussels, Belgium., Boumahd Y; Metastasis Research Laboratory, GIGA-Cancer, GIGA Institute, University of Liège, Liège, Belgium., Gasmi I; Metastasis Research Laboratory, GIGA-Cancer, GIGA Institute, University of Liège, Liège, Belgium., Crake R; Metastasis Research Laboratory, GIGA-Cancer, GIGA Institute, University of Liège, Liège, Belgium., Bellier J; Metastasis Research Laboratory, GIGA-Cancer, GIGA Institute, University of Liège, Liège, Belgium., Nokin MJ; Metastasis Research Laboratory, GIGA-Cancer, GIGA Institute, University of Liège, Liège, Belgium., Calonne E; Laboratory of Cancer Epigenetics, Faculty of Medicine, ULB-Cancer Research Center (U-CRC), Université Libre de Bruxelles (ULB), Brussels, Belgium., Deplus R; Laboratory of Cancer Epigenetics, Faculty of Medicine, ULB-Cancer Research Center (U-CRC), Université Libre de Bruxelles (ULB), Brussels, Belgium., Wissocq T; Metastasis Research Laboratory, GIGA-Cancer, GIGA Institute, University of Liège, Liège, Belgium., Peulen O; Metastasis Research Laboratory, GIGA-Cancer, GIGA Institute, University of Liège, Liège, Belgium., Castronovo V; Metastasis Research Laboratory, GIGA-Cancer, GIGA Institute, University of Liège, Liège, Belgium., Fuks F; Laboratory of Cancer Epigenetics, Faculty of Medicine, ULB-Cancer Research Center (U-CRC), Université Libre de Bruxelles (ULB), Brussels, Belgium.; WELBIO (Walloon Excellence in Lifesciences & Biotechnology), Brussels, Belgium., Bellahcène A; Metastasis Research Laboratory, GIGA-Cancer, GIGA Institute, University of Liège, Liège, Belgium. a.bellahcene@uliege.be. |
| المصدر: | Journal of experimental & clinical cancer research : CR [J Exp Clin Cancer Res] 2023 Mar 31; Vol. 42 (1), pp. 78. Date of Electronic Publication: 2023 Mar 31. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: BioMed Central Country of Publication: England NLM ID: 8308647 Publication Model: Electronic Cited Medium: Internet ISSN: 1756-9966 (Electronic) Linking ISSN: 03929078 NLM ISO Abbreviation: J Exp Clin Cancer Res Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2009- : London : BioMed Central Original Publication: [Roma] : APSIT, |
| مواضيع طبية MeSH: | DNA Methylation* , Triple Negative Breast Neoplasms*/metabolism, Humans ; Pyruvaldehyde/metabolism ; Cell Line, Tumor ; Transcriptome ; Gene Expression Regulation, Neoplastic |
| مستخلص: | Background: Aerobic glycolysis, also known as the Warburg effect, is predominantly upregulated in a variety of solid tumors, including breast cancer. We have previously reported that methylglyoxal (MG), a very reactive by-product of glycolysis, unexpectedly enhanced the metastatic potential in triple negative breast cancer (TNBC) cells. MG and MG-derived glycation products have been associated with various diseases, such as diabetes, neurodegenerative disorders, and cancer. Glyoxalase 1 (GLO1) exerts an anti-glycation defense by detoxifying MG to D-lactate. Methods: Here, we used our validated model consisting of stable GLO1 depletion to induce MG stress in TNBC cells. Using genome-scale DNA methylation analysis, we report that this condition resulted in DNA hypermethylation in TNBC cells and xenografts. Results: GLO1-depleted breast cancer cells showed elevated expression of DNMT3B methyltransferase and significant loss of metastasis-related tumor suppressor genes, as assessed using integrated analysis of methylome and transcriptome data. Interestingly, MG scavengers revealed to be as potent as typical DNA demethylating agents at triggering the re-expression of representative silenced genes. Importantly, we delineated an epigenomic MG signature that effectively stratified TNBC patients based on survival. Conclusion: This study emphasizes the importance of MG oncometabolite, occurring downstream of the Warburg effect, as a novel epigenetic regulator and proposes MG scavengers to reverse altered patterns of gene expression in TNBC. (© 2023. The Author(s).) |
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| معلومات مُعتمدة: | PDR T.0188.18 Fonds De La Recherche Scientifique - FNRS; PDR T.0188.18 Fonds De La Recherche Scientifique - FNRS; Télévie 7.4541.17 Fonds De La Recherche Scientifique - FNRS; Télévie 7.4541.17 Fonds De La Recherche Scientifique - FNRS; AUWB-2018-2023 Action de recherche concertée; FCC 2016-086 Fondation contre le Cancer |
| فهرسة مساهمة: | Keywords: Breast cancer; DNA methylation; Metastasis; Methylglyoxal; Tumor suppressor genes |
| المشرفين على المادة: | 722KLD7415 (Pyruvaldehyde) |
| تواريخ الأحداث: | Date Created: 20230330 Date Completed: 20230403 Latest Revision: 20230403 |
| رمز التحديث: | 20230403 |
| مُعرف محوري في PubMed: | PMC10064647 |
| DOI: | 10.1186/s13046-023-02637-w |
| PMID: | 36998085 |
| قاعدة البيانات: | MEDLINE |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 1756-9966 |
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| DOI: | 10.1186/s13046-023-02637-w |