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DNA Methylation assessment of GLO1-depleted MDA-MB-231 breast cancer cells and mouse xenografts

ABSTRACT: Oncometabolites are of the utmost importance to our understanding of tumor initiation, progression and resistance to therapy. We previously demonstrated that methylglyoxal (MG), a reactive dicarbonyl spontaneously formed in glycolytic cancer cells, unexpectedly enhanced their metastatic potential. Here, using genome-wide DNA methylation analysis, we report that MG stress induced DNA methyltransferases (DNMTs) expression resulting in DNA hypermethylation in triple negative breast cancer cells. Interestingly, we observed that DNMT3B protein was stabilized upon MG stress. Consistently, MG stressed cells demonstrated a significant loss of tumor suppressor genes as assessed using integrated analysis of methylome and RNASeq data. Both 5-AZA demethylating agent and MG scavengers triggered the re-expression of representative silenced genes. We have delineated an epigenomic signature of MG stress that effectively provided survival stratification in breast cancer patients. This study emphasizes the importance of MG stress, occurring downstream of the Warburg effect, as a major epigenetic regulator and proposes MG scavengers to reverse altered patterns of gene expression associated with MG stress pro-cancer effects.

ORGANISM(S): Homo sapiens

PROVIDER: GSE185237 | GEO | 2022/10/01

REPOSITORIES: GEO

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