Cuproptosis, the novel type of oxidation-induced cell death in thoracic cancers: can it enhance the success of immunotherapy?

Cell Communication and Signaling, Год журнала: 2024, Номер 22(1)

Опубликована: Июль 27, 2024

Abstract Copper is an important metal micronutrient, required for the balanced growth and normal physiological functions of human organism. Copper-related toxicity dysbalanced metabolism were associated with disruption intracellular respiration development various diseases, including cancer. Notably, copper-induced cell death was defined as cuproptosis which also observed in malignant cells, representing attractive anti-cancer instrument. Excess copper leads to aggregation lipoylation proteins toxic stress, ultimately resulting activation death. Differential expression cuproptosis-related genes detected tissues. Cuproptosis-related linked regulation oxidative immune responses, composition tumor microenvironment. Activation increased redox-metabolism-regulating genes, such ferredoxin 1 (FDX1), lipoic acid synthetase (LIAS), lipoyltransferase (LIPT1), dihydrolipoamide dehydrogenase (DLD), drolipoamide S-acetyltransferase (DLAT), pyruvate E1 subunit alpha (PDHA1), beta (PDHB)). Accordingly, copper-activated network suggested target cancer therapy. Mechanisms different cancers microenvironment are discussed this study. The analysis current findings indicates that therapeutic signaling, targets may provide effective tool improvement immunotherapy regimens. Graphical

Язык: Английский

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Adrenomedullin/FOXO3 enhances sunitinib resistance in clear cell renal cell carcinoma by inhibiting FDX1 expression and cuproptosis

The FASEB Journal, Год журнала: 2023, Номер 37(10)

Опубликована: Сен. 12, 2023

Abstract Cuproptosis, a new type of copper‐induced cell death, is involved in the antitumor activity and resistance multiple chemotherapeutic drugs. Our previous study revealed that adrenomedullin (ADM) was engaged sunitinib clear renal carcinoma (ccRCC). However, it has yet to be investigated whether how ADM regulates by cuproptosis. This found expression elevated sunitinib‐resistant ccRCC tissues cells. Furthermore, upregulation significantly enhanced chemoresistance compared with their respective control. Moreover, cuproptosis ADM‐regulated inhibiting mammalian ferredoxin 1 (FDX1) expression. Mechanically, upregulated activates p38/MAPK signaling pathway promote Forkhead box O3 (FOXO3) phosphorylation its entry into nucleus. Consequently, increased FOXO3 nucleus inhibited FDX1 transcription cuproptosis, promoting chemoresistance. Collectively, critical effector role progress thus relevant target eradicate population resistance.

Язык: Английский

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Copper-mediated novel cell death pathway in tumor cells and implications for innovative cancer therapies

Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 168, С. 115730 - 115730

Опубликована: Окт. 19, 2023

Previous investigations have unraveled an array of cellular demise modalities, encompassing apoptosis, necrosis, pyroptosis, iron death, and several others. These diverse pathways cell death been harnessed as therapeutic strategies for eradicating tumor cells. Recent scientific inquiries unveiled a novel mode namely copper which is contingent upon intracellular levels. Diverging from conventional mechanisms, exhibits heightened reliance on mitochondrial respiration, specifically the tricarboxylic acid (TCA) cycle. Tumor cells exhibit distinctive metabolic profiles elevated content compared to their normal counterparts. The emergence presents tantalizing prospect targeted therapies in realm cancer treatment. Thus, primary objective this review introduce proteins intricate mechanisms underlying while comprehensively summarizing extensive body knowledge concerning its ramifications across types. insights garnered comprehensive synthesis will serve invaluable reference driving development tailor-made interventions tumors.

Язык: Английский

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MicroRNA-21 in urologic cancers: from molecular mechanisms to clinical implications

Frontiers in Cell and Developmental Biology, Год журнала: 2024, Номер 12

Опубликована: Июль 23, 2024

The three most common kinds of urologic malignancies are prostate, bladder, and kidney cancer, which typically cause substantial morbidity mortality. Early detection effective treatment essential due to their high fatality rates. As a result, there is an urgent need for innovative research improve the clinical management patients with cancers. A type small noncoding RNAs 22 nucleotides, microRNAs (miRNAs) well-known important roles in variety developmental processes. Among these, microRNA-21 (miR-21) stands out as commonly studied miRNA implications tumorigenesis cancer development, particularly urological tumors. Recent has shed light on dysregulation miR-21 tumors, offering insights into its potential prognostic, diagnostic, therapeutic tool. This review delves pathogenesis renal cancers, utility biomarker, possibilities targeting miR-21.

Язык: Английский

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Cuproptosis in microsatellite stable colon cancer cells affects the cytotoxicity of CD8+T through the WNT signaling pathway

Chemico-Biological Interactions, Год журнала: 2024, Номер 403, С. 111239 - 111239

Опубликована: Сен. 19, 2024

Язык: Английский

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Machine learning-driven prognostic analysis of cuproptosis and disulfidptosis-related lncRNAs in clear cell renal cell carcinoma: a step towards precision oncology

European journal of medical research, Год журнала: 2024, Номер 29(1)

Опубликована: Март 16, 2024

Cuproptosis and disulfidptosis, recently discovered mechanisms of cell death, have demonstrated that differential expression key genes long non-coding RNAs (lncRNAs) profoundly influences tumor development affects their drug sensitivity. Clear renal carcinoma (ccRCC), the most common subtype kidney cancer, presently lacks research utilizing cuproptosis disulfidptosis-related lncRNAs (CDRLRs) as prognostic markers. In this study, we analyzed RNA-seq data, clinical information, mutation data from The Cancer Genome Atlas (TCGA) on ccRCC cross-referenced it with known (CDRGs). Using LASSO machine learning algorithm, identified four CDRLRs-ACVR2B-AS1, AC095055.1, AL161782.1, MANEA-DT-that are strongly associated prognosis used them to construct a risk model. To verify model's reliability validate these CDRLRs significant factors, performed dataset grouping validation, followed by RT-qPCR external database validation for in ccRCC. Gene function pathway analysis were conducted using Ontology (GO) Set Enrichment Analysis (GSEA) high- low-risk groups. Additionally, burden (TMB) immune microenvironment (TME), employing oncoPredict Immunophenoscore (IPS) algorithms assess sensitivity diverse categories targeted therapeutics immunosuppressants. Our predominant objective is refine predictions patients inform treatment decisions conducting an exhaustive study disulfidptosis.

Язык: Английский

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Copper homeostasis and copper-induced cell death in tumor immunity: implications for therapeutic strategies in cancer immunotherapy

Biomarker Research, Год журнала: 2024, Номер 12(1)

Опубликована: Окт. 31, 2024

Copper is an important trace element for maintaining key biological functions such as cellular respiration, nerve conduction, and antioxidant defense. Maintaining copper homeostasis critical human health, its imbalance has been linked to various diseases, especially cancer. Cuproptosis, a novel mechanism of copper-induced cell death, provides new therapeutic opportunities metal ion regulation interact with fate. This review insights into the complex mechanisms metabolism, molecular basis cuproptosis, association cancer development. We assess role cuproptosis-related genes (CRGs) associated tumorigenesis, their importance prognostic indicators targets, impact on tumor microenvironment (TME) immune response. Ultimately, this highlights interplay between copper, immunotherapy.

Язык: Английский

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Post-transcriptional regulation of tumor suppressor gene lncRNA CARMN via m6A modification and miRNA regulation in cervical cancer

Journal of Cancer Research and Clinical Oncology, Год журнала: 2023, Номер 149(12), С. 10307 - 10318

Опубликована: Июнь 5, 2023

Язык: Английский

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METTL3 promotes Non-Small-Cell Lung Cancer Growth and Metastasis by Inhibiting FDX1 Through Copper Death-Associated Pri-miR-21-5p Maturation

Epigenomics, Год журнала: 2023, Номер 15(23), С. 1237 - 1255

Опубликована: Дек. 1, 2023

We probed into the significance of METTL3 in maturation process pri-miR-21-5p. specifically investigated its impact on regulation FDX1 and involvement progression non-small-cell lung cancer (NSCLC).

Язык: Английский

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Copper homeostasis and cuproptosis‐related genes: Therapeutic perspectives in non‐alcoholic fatty liver disease

Diabetes Obesity and Metabolism, Год журнала: 2024, Номер 26(11), С. 4830 - 4845

Опубликована: Сен. 4, 2024

Non-alcoholic fatty liver disease (NAFLD), a metabolic-associated disease, has become the most common chronic worldwide. Recently, discovery of cuproptosis, newly identified mode cell death, further highlighted importance copper in maintaining metabolic homeostasis. An increasing number studies have confirmed that metabolism is closely related to pathogenesis NAFLD. However, relationship between NAFLD and metabolism, especially remains unclear. In this review, we aim summarize current understanding its dysregulation, particularly role dysregulation More importantly, review emphasizes potential gene-targeted therapeutic strategies, challenges future cuproptosis-related genes treatment This aims provide innovative strategies for

Язык: Английский

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