From Metabolism to Genetics and Vice Versa: The Rising Role of Oncometabolites in Cancer Development and Therapy

Gregorio, Emanuela Di; Miolo, Gianmaria; Saorin, Asia; Steffan, Agostino; Corona, Giuseppe

doi:10.3390/ijms22115574

Cited by 7 publications

(5 citation statements)

References 244 publications

(270 reference statements)

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“…6 ). In order to adapt to rapid proliferation and differentiation, the information transmission and material transformation between or within tumor cells must increase significantly, and energy conversion needs to be reconstructed, creating a microenvironment suitable for tumor cell survival, enhancing the ability of invasion and metastasis, and also helping tumor cells to escape the body’s immune system and apoptosis mechanisms [ 40 ]. m6A-related genes are closely related to tumor metabolism [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

N6-methyladenosine-related lncRNAs is a potential marker for predicting prognosis and immunotherapy in ovarian cancer

Nie

Tan

2022

Hereditas

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Background With a lack of specific symptoms, ovarian cancer (OV) is often diagnosed at an advanced stage. This coupled with inadequate prognostic indicators and treatments with limited therapeutic effect make OV the deadliest type of gynecological tumor. Recent research indicates that N6-methyladenosine (m6A) and long-chain non-coding RNA (lncRNA) play important roles in the prognosis of OV and the efficacy of immunotherapy. Results Using the Cancer Genome Atlas (TCGA) OV-related data set and the expression profiles of 21 m6A-related genes, we identified two m6A subtypes, and the differentially expressed genes between the two. Based on the differentially expressed lncRNAs in the two m6A subtypes and the lncRNAs co-expressed with the 21 m6A-related genes, single-factor cox and LASSO regression were used to further isolate the 13 major lncRNAs. Finally, multi-factor cox regression was used to construct a m6A-related lncRNA risk score model for OV, with good performance in patient prognosis. Using risk score, OV tumor samples are divided into with high- and low-score groups. We explored the differences in clinical characteristics, tumor mutational burden, and tumor immune cell infiltration between the two groups, and evaluated the risk score’s ability to predict the benefit of immunotherapy. Conclusion Our m6A-based lncRNA risk model could be used to predict the prognosis and immunotherapy response of future OV patients.

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Section: Discussionmentioning

confidence: 99%

N6-methyladenosine-related lncRNAs is a potential marker for predicting prognosis and immunotherapy in ovarian cancer

Nie

Tan

2022

Hereditas

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“…Finally, three key oncometabolites (2-hydroxyglutarate, succinate, and fumarate) drive malignant transformation primarily through methylation regulation and pseudohypoxic signaling. They serve as structural mimetics to α-KG and thus competitively inhibit protein, DNA, and RNA demethylases and proline hydroxylases belonging to the superfamily of α-KG-dependent dioxygenases [ 44 , 45 ]. Indeed, genome-wide methylation landscape studies identified a new epigenetic CpG methylator phenotype (CMP) subtype of mCRPC, which is enriched for mutually exclusive mutations in TET2 and IDH1 [ 301 ].…”

Section: Metabolites and Gene Regulationmentioning

confidence: 99%

“…2-HG producing-mutations in IDH1 are associated with CpG island hyper-methylations in the Cancer Genome Atlas (TCGA) primary PCa database [ 306 ]. It remains to be answered how germline SDH and FH mutations exhibit a high degree of tissue specificity in the patients without drastic adverse effects in most other tissues [ 44 , 45 , 307 ].…”

Section: Metabolites and Gene Regulationmentioning

confidence: 99%

“…The situation drastically changed when the link between oncogenic drivers and metabolic reprogramming began to be appreciated in the early 2000s [ 39 , 40 , 41 , 42 , 43 ]. Altered metabolism not only supports and maintains tumor phenotypes by meeting their energetic and metabolic demands, it also allows for further progression to metastases [ 44 , 45 ]. Metabolic reprogramming is now firmly established as a hallmark of cancer and is attractive because it represents unique vulnerabilities that can be therapeutically targeted [ 39 , 41 ].…”

Section: Introductionmentioning

confidence: 99%

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Druggable Metabolic Vulnerabilities Are Exposed and Masked during Progression to Castration Resistant Prostate Cancer

et al. 2022

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There is an urgent need for exploring new actionable targets other than androgen receptor to improve outcome from lethal castration-resistant prostate cancer. Tumor metabolism has reemerged as a hallmark of cancer that drives and supports oncogenesis. In this regard, it is important to understand the relationship between distinctive metabolic features, androgen receptor signaling, genetic drivers in prostate cancer, and the tumor microenvironment (symbiotic and competitive metabolic interactions) to identify metabolic vulnerabilities. We explore the links between metabolism and gene regulation, and thus the unique metabolic signatures that define the malignant phenotypes at given stages of prostate tumor progression. We also provide an overview of current metabolism-based pharmacological strategies to be developed or repurposed for metabolism-based therapeutics for castration-resistant prostate cancer.

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“…It can be affected by intrinsic or extrinsic stimuli, including secreted metabolites (oncometabolites) from cancer cells themselves, the cancer tissue microenvironment, the extracellular matrix, and the breast microbiome (part of the breast microenvironment) [ 7 , 20 , 21 , 22 ]. Multiple studies that identified oncometabolites and their associations with cancer progression were extensively reviewed in [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

E. coli Secretome Metabolically Modulates MDA-MB-231 Breast Cancer Cells’ Energy Metabolism

AlMalki

Sebaa

Al-Ansari

et al. 2023

IJMS

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Breast cancer (BC) is commonly diagnosed in women. BC cells are associated with altered metabolism, which is essential to support their energetic requirements, cellular proliferation, and continuous survival. The altered metabolism of BC cells is a result of the genetic abnormalities of BC cells. Risk factors can also enhance it, including age, lifestyle, hormone disturbances, etc. Other unknown BC-promoting risk factors are under scientific investigation. One of these investigated factors is the microbiome. However, whether the breast microbiome found in the BC tissue microenvironment can impact BC cells has not been studied. We hypothesized that E. coli, part of a normal breast microbiome with more presence in BC tissue, secretes metabolic molecules that could alter BC cells’ metabolism to maintain their survival. Thus, we directly examined the impact of the E. coli secretome on the metabolism of BC cells in vitro. MDA-MB-231 cells, an in vitro model of aggressive triple-negative BC cells, were treated with the E. coli secretome at different time points, followed by untargeted metabolomics analyses via liquid chromatography–mass spectrometry to identify metabolic alterations in the treated BC cell lines. MDA-MB-231 cells that were not treated were used as controls. Moreover, metabolomic analyses were performed on the E. coli secretome to profile the most significant bacterial metabolites affecting the metabolism of the treated BC cell lines. The metabolomics results revealed about 15 metabolites that potentially have indirect roles in cancer metabolism that were secreted from E. coli in the culture media of MDA-MB-231 cells. The cells treated with the E. coli secretome showed 105 dysregulated cellular metabolites compared to controls. The dysregulated cellular metabolites were involved in the metabolism of fructose and mannose, sphingolipids, amino acids, fatty acids, amino sugar, nucleotide sugar, and pyrimidine, which are vital pathways required for the pathogenesis of BC. Our findings are the first to show that the E. coli secretome modulates the BC cells’ energy metabolism, highlighting insights into the possibility of altered metabolic events in BC tissue in the actual BC tissue microenvironment that are potentially induced by the local bacteria. Our study provides metabolic data that could be as a basis for future studies searching for the underlying mechanisms mediated by bacteria and their secretome to alter the metabolism of BC cells.

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From Metabolism to Genetics and Vice Versa: The Rising Role of Oncometabolites in Cancer Development and Therapy

Cited by 7 publications

References 244 publications

N6-methyladenosine-related lncRNAs is a potential marker for predicting prognosis and immunotherapy in ovarian cancer

N6-methyladenosine-related lncRNAs is a potential marker for predicting prognosis and immunotherapy in ovarian cancer

Druggable Metabolic Vulnerabilities Are Exposed and Masked during Progression to Castration Resistant Prostate Cancer

E. coli Secretome Metabolically Modulates MDA-MB-231 Breast Cancer Cells’ Energy Metabolism

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