Cuproptosis and cuproptosis-related genes: Emerging potential therapeutic targets in breast cancer

Liu, Xiangdong; Luo, Bo; Wu, Xinhong; Tang, Zijian

doi:10.1016/j.bbcan.2023.189013

Cited by 16 publications

(2 citation statements)

References 133 publications

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“…Cuproptosis, a recently identified form of regulatory cell death, results from excessive copper accumulation and is closely associated with breast cancer proliferation and metastasis [149,150]. Copper is involved in cell proliferation, angiogenesis and metastasis and influences the progression of breast cancer [151]. Due to their wide range of catalytic functions and electrochemical activity [152], copper complexes can have tumor inhibitory effects by inducing ROS production, glutathione depletion, proteasome inhibition and DNA damage [153].…”

Section: Heavy Metals and Oxidative Stress In Breast Cancermentioning

confidence: 99%

Oxidative Stress in Breast Cancer: A Biochemical Map of Reactive Oxygen Species Production

Bel’skaya,

Dyachenko

2024

CIMB

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This review systematizes information about the metabolic features of breast cancer directly related to oxidative stress. It has been shown those redox changes occur at all levels and affect many regulatory systems in the human body. The features of the biochemical processes occurring in breast cancer are described, ranging from nonspecific, at first glance, and strictly biochemical to hormone-induced reactions, genetic and epigenetic regulation, which allows for a broader and deeper understanding of the principles of oncogenesis, as well as maintaining the viability of cancer cells in the mammary gland. Specific pathways of the activation of oxidative stress have been studied as a response to the overproduction of stress hormones and estrogens, and specific ways to reduce its negative impact have been described. The diversity of participants that trigger redox reactions from different sides is considered more fully: glycolytic activity in breast cancer, and the nature of consumption of amino acids and metals. The role of metals in oxidative stress is discussed in detail. They can act as both co-factors and direct participants in oxidative stress, since they are either a trigger mechanism for lipid peroxidation or capable of activating signaling pathways that affect tumorigenesis. Special attention has been paid to the genetic and epigenetic regulation of breast tumors. A complex cascade of mechanisms of epigenetic regulation is explained, which made it possible to reconsider the existing opinion about the triggers and pathways for launching the oncological process, the survival of cancer cells and their ability to localize.

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Section: Heavy Metals and Oxidative Stress In Breast Cancermentioning

confidence: 99%

Oxidative Stress in Breast Cancer: A Biochemical Map of Reactive Oxygen Species Production

Bel’skaya,

Dyachenko

2024

CIMB

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“…Considering the crucial role of glycolysis in cancer cell survival and proliferation, copper-based therapies may reduce the malignant potential of cancer cells. Emerging evidence emphasizes the growing importance of coproptosis-related genes in the clinical diagnosis and treatment of breast cancer 7 . The copper ionophore elelesclomol, which transports copper ions, disrupts the FDX1-mediated synthesis of Fe–S cluster proteins.…”

Section: Introductionmentioning

confidence: 99%

Identification and validation of a copper homeostasis-related gene signature for the predicting prognosis of breast cancer patients via integrated bioinformatics analysis

Li,

Wei,

Wang

et al. 2024

Sci Rep

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The prognostic value of copper homeostasis-related genes in breast cancer (BC) remains largely unexplored. We analyzed copper homeostasis-related gene profiles within The Cancer Genome Atlas Program breast cancer cohorts and performed correlation analysis to explore the relationship between copper homeostasis-related mRNAs (chrmRNA) and lncRNAs. Based on these results, we developed a gene signature-based risk assessment model to predict BC patient outcomes using Cox regression analysis and a nomogram, which was further validated in a cohort of 72 BC patients. Using the gene set enrichment analysis, we identified 139 chrmRNAs and 16 core mRNAs via the Protein–Protein Interaction network. Additionally, our copper homeostasis-related lncRNAs (chrlncRNAs) (PINK1.AS, OIP5.AS1, HID.AS1, and MAPT.AS1) were evaluated as gene signatures of the predictive model. Kaplan–Meier survival analysis revealed that patients with a high-risk gene signature had significantly poorer clinical outcomes. Receiver operating characteristic curves showed that the prognostic value of the chrlncRNAs model reached 0.795 after ten years. Principal component analysis demonstrated the capability of the model to distinguish between low- and high-risk BC patients based on the gene signature. Using the pRRophetic package, we screened out 24 anticancer drugs that exhibited a significant relationship with the predictive model. Notably, we observed higher expression levels of the four chrlncRNAs in tumor tissues than in the adjacent normal tissues. The correlation between our model and the clinical characteristics of patients with BC highlights the potential of chrlncRNAs for predicting tumor progression. This novel gene signature not only predicts the prognosis of patients with BC but also suggests that targeting copper homeostasis may be a viable treatment strategy.

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DLD is a potential therapeutic target for COVID-19 infection in diffuse large B-cell lymphoma patients

Chen,

Kang,

Chen

et al. 2024

Apoptosis

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Since the discovery of copper induces cell death(cuprotosis) in 2022, it has been one of the biggest research hotspots. cuprotosis related genes (CRGs) has been demonstrated to be a potential therapeutic target for cancer, however, the molecular mechanism of CRGs in coronavirus disease 2019 (COVID-19) infected in DLBCL patients has not been reported yet. Therefore, our research objective is first to elucidate the mechanism and role of CRGs in COVID-19. Secondly, we conducted univariate and multivariate analysis and machine learning to screen for CRGs with common expression differences in COVID-19 and DLBCL. Finally, the functional role and immune mechanism of genes in DLBCL were confirmed through cell experiments and immune analysis. The research results show that CRGs play an important role in the occurrence and development of COVID-19. Univariate analysis and machine learning confirm that dihydrolipoamide dehydrogenase (DLD) is the common key gene of COVID-19 and DLBCL. Inhibiting the expression of DLD can significantly inhibit the cycle progression and promote cell apoptosis of DLBCL cells and can target positive regulation of Lysine-specific demethylase 1 (LSD1, also known as KDM1A) to inhibit the proliferation of DLBCL cells and promote cell apoptosis. The immune analysis results show that high-expression of DLD may reduce T cell-mediated anti-tumor immunity by regulating immune infiltration of CD8 + T cells and positively regulating immune checkpoints LAG3 and CD276. Reducing the expression of DLD can effectively enhance T cell-mediated anti-tumor immunity, thereby clearing cancer cells and preventing cancer growth. In conclusion, DLD may be a potential therapeutic target for COVID-19 infection in DLBCL patients. Our research provides a theoretical basis for improving the clinical treatment of COVID-19 infection in DLBCL.

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Cuproptosis and cuproptosis-related genes: Emerging potential therapeutic targets in breast cancer

Cited by 16 publications

References 133 publications

Oxidative Stress in Breast Cancer: A Biochemical Map of Reactive Oxygen Species Production

Oxidative Stress in Breast Cancer: A Biochemical Map of Reactive Oxygen Species Production

Identification and validation of a copper homeostasis-related gene signature for the predicting prognosis of breast cancer patients via integrated bioinformatics analysis

DLD is a potential therapeutic target for COVID-19 infection in diffuse large B-cell lymphoma patients

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