Cuproptosis: mechanisms and links with cancers

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: March 7, 2023

Abstract Cuproptosis was a copper-dependent and unique kind of cell death that separate from existing other forms death. The last decade has witnessed considerable increase in investigations programmed death, whether copper induced an independent form long been argued until mechanism cuproptosis revealed. After that, increasing number researchers attempted to identify the relationship between process cancer. Thus, this review, we systematically detailed systemic cellular metabolic processes copper-related tumor signaling pathways. Moreover, not only focus on discovery its mechanism, but also outline association cancers. Finally, further highlight possible therapeutic direction employing ion ionophores with cuproptosis-inducing functions combination small molecule drugs for targeted therapy treat specific

Language: Английский

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Copper homeostasis and cuproptosis in mitochondria

Life Sciences, Journal Year: 2023, Volume and Issue: 334, P. 122223 - 122223

Published: Oct. 29, 2023

Language: Английский

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Crosstalk between metabolism and cell death in tumorigenesis

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: April 4, 2024

Abstract It is generally recognized that tumor cells proliferate more rapidly than normal cells. Due to such an abnormally rapid proliferation rate, cancer constantly encounter the limits of insufficient oxygen and nutrient supplies. To satisfy their growth needs resist adverse environmental events, modify metabolic pathways produce both extra energies substances required for growth. Realizing characters special will be helpful eliminating them during therapy. Cell death a hot topic long-term study targeting cell one most effective ways repress Many studies have successfully demonstrated metabolism inextricably linked Here we summarize recently identified specifically impact on different types deaths discuss roles in tumorigenesis.

Language: Английский

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Construction and validation of a cuproptosis-related prognostic model for glioblastoma

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 6, 2023

Cuproptosis, a newly reported type of programmed cell death, takes part in the regulation tumor progression, treatment response, and prognosis. But specific effect cuproptosis-related genes (CRGs) on glioblastoma (GBM) is still unclear.The transcriptome data corresponding clinical GBM samples were downloaded from TCGA GEO databases. R software packages used to perform statistical analysis, consensus cluster survival Cox regression Lasso microenvironment analysis. The mRNA protein expression levels model-related detected by RT-qPCR Western blot assays, respectively.The profile CRGs 209 two separate datasets was obtained. Two cuproptosis subtypes, CRGcluster A B, identified There apparent differences prognosis, microenvironment, immune checkpoint between there 79 prognostic differentially expressed (DEGs). According DEGs, gene geneCluster identified, risk score model constructed validated. This consists five including PDIA4, DUSP6, PTPRN, PILRB, CBLN1. Ultimately, improve applicability model, nomogram established. Patients with low-risk have higher mutation burden predict longer OS than high-risk group. Moreover, related drug sensitivity negatively correlated CSC index.We successfully which can independently prognosis patients. These results further complement understanding provide new theoretical support for developing more effective strategy.

Language: Английский

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Role of cuproptosis in understanding diseases

Human Cell, Journal Year: 2023, Volume and Issue: 36(4), P. 1244 - 1252

Published: May 8, 2023

Language: Английский

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Cuproptosis-related lncRNA signature as a prognostic tool and therapeutic target in diffuse large B cell lymphoma

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: June 5, 2024

Abstract Cuproptosis is a newly defined form of programmed cell death that relies on mitochondria respiration. Long noncoding RNAs (lncRNAs) play crucial roles in tumorigenesis and metastasis. However, whether cuproptosis-related lncRNAs are involved the pathogenesis diffuse large B lymphoma (DLBCL) remains unclear. This study aimed to identify prognostic signatures DLBCL investigate their potential molecular functions. RNA-Seq data clinical information for were collected from The Cancer Genome Atlas (TCGA) Gene Expression Omnibus (GEO). Cuproptosis-related screened out through Pearson correlation analysis. Utilizing univariate Cox, least absolute shrinkage selection operator (Lasso) multivariate Cox regression analysis, we identified seven developed risk prediction model evaluate its value across multiple groups. GO KEGG functional analyses, single-sample GSEA (ssGSEA), ESTIMATE algorithm used analyze mechanisms immune status between different Additionally, drug sensitivity analysis drugs with efficacy DLBCL. Finally, protein–protein interaction (PPI) network constructed based weighted gene co-expression (WGCNA). We set including LINC00294, RNF139-AS1, LINC00654, WWC2-AS2, LINC00661, LINC01165 LINC01398, which high-risk group was associated shorter survival time than low-risk group, signature-based score demonstrated superior ability patients compared traditional features. By analyzing landscapes two groups, found immunosuppressive types significantly increased group. Moreover, enrichment highlighted association differentially expressed genes metabolic, inflammatory immune-related pathways patients. also showed more vinorelbine pyrimethamine. A lncRNA signature established predict prognosis provide insights into therapeutic strategies

Language: Английский

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Multiomics Analysis Reveals Cuproptosis-Related Signature for Evaluating Prognosis and Immunotherapy Efficacy in Colorectal Cancer

Cancers, Journal Year: 2023, Volume and Issue: 15(2), P. 387 - 387

Published: Jan. 6, 2023

Cuproptosis is a copper-induced form of mitochondrial cell death which engaged in the proliferation and migration variety tumors. Nevertheless, role cuproptosis tumor microenvironment (TME) remodeling antitumor therapy still poorly understood. We characterized two diverse cuproptosis-associated molecular isoforms CRC exhibit distinct prognostic TME characteristics. Subsequently, we constructed model containing five genes divided patients into high CPS-score group low group. Univariate multivariate Cox analyses showed that CPS score could be used as an independent factor. The nomogram, its consequent calibration curves, indicated this signature had good predictive power for CRC. analysis single-cell sequencing data significant expression HES4 SPHK1 various immune stromal (including fibroblasts) cells. Further studies mutational burden (TMB), microsatellite instability (MSI-H) ratio, checkpoint blockade (ICB), human leukocyte antigen (HLA) gene all positively correlated with score, predicting better reaction to immunotherapy CPS-core patients. from subtypes can tool evaluate prognosis their response immunotherapy.

Language: Английский

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Cuproptosis-related lncRNA signature for prognostic prediction in patients with acute myeloid leukemia

BMC Bioinformatics, Journal Year: 2023, Volume and Issue: 24(1)

Published: Feb. 3, 2023

Long non-coding RNAs (lncRNAs) have been reported to a crucial impact on the pathogenesis of acute myeloid leukemia (AML). Cuproptosis, copper-triggered modality mitochondrial cell death, might serve as promising therapeutic target for cancer treatment and clinical outcome prediction. Nevertheless, role cuproptosis-related lncRNAs in AML is not fully understood.The RNA sequencing data demographic characteristics patients were downloaded from The Cancer Genome Atlas database. Pearson correlation analysis, least absolute shrinkage selection operator algorithm, univariable multivariable Cox regression analyses applied identify lncRNA signature determine its feasibility prognosis performance proposed was evaluated via Kaplan-Meier survival receiver operating characteristic curves, principal component analysis. Functional analysis implemented uncover potential prognostic mechanisms. Additionally, quantitative real-time PCR (qRT-PCR) employed validate expression samples.A consisting seven (namely NFE4, LINC00989, LINC02062, AC006460.2, AL353796.1, PSMB8-AS1, AC000120.1) proposed. Multivariable cox revealed that an independent factor AML. Notably, nomogram based this showed excellent accuracy predicting 1-, 3-, 5-year (area under curve = 0.846, 0.801, 0.895, respectively). results suggested existence significant association between immune-related pathways. pattern validated samples.Collectively, we constructed prediction model prognosis. obtained risk score may reveal immunotherapy response with disease.

Language: Английский

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A cuproptosis score model and prognostic score model can evaluate clinical characteristics and immune microenvironment in NSCLC

Cancer Cell International, Journal Year: 2024, Volume and Issue: 24(1)

Published: Feb. 10, 2024

Abstract Background Cuproptosis-related genes (CRGs) are associated with lung adenocarcinoma. However, the links between CRGs and non-small-cell cancer (NSCLC) not clear. In this study, we aimed to develop two cuproptosis models investigate their correlation NSCLC in terms of clinical features tumor microenvironment. Methods CRG expression profiles data from normal tissues was obtained GEO (GSE42127) TCGA datasets. Molecular clusters were classified into three patterns based on cluster-related specific differentially expressed (CRDEGs). Then, established. First, a prognostic score model CRDEGs established using univariate/multivariate Cox analysis. through principal component analysis, prognosis-related acquired via univariate analysis CRDEGs. patients divided high/low risk groups. Results Eighteen acquired, all upregulated tissues, 15 which significantly ( P < 0.05). Among clusters, cluster B had best prognosis. CRDEG C survival. model, high-risk group worse prognosis, higher mutation load, lower immune infiltration while high represented better survival, high-level infiltration. Conclusions The may be prognosis These novel findings progression landscape facilitate provision more personalized immunotherapy interventions for patients.

Language: Английский

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Lidocaine could promote the cuproptosis through up-regulating the long noncoding RNA DNMBP-AS1 in Hep-2 cells

BMC Cancer, Journal Year: 2025, Volume and Issue: 25(1)

Published: Jan. 22, 2025

Abstract Background Lidocaine is a traditional local anesthetic, which has been reported to trigger apoptosis through the mitochondrial pathway, independent of death receptor signaling. Cuproptosis copper triggered cell mode. In this study, we explored biological effects lidocaine on cuproptosis in Hep-2 cells and studied relevant mechanisms. Methods quantitative RT-PCR was used measure expression level long noncoding RNA (IncRNA) DNMBP-AS1. DNMBP-AS1 siRNA (si-DNMBP-AS1) were transfected into verify roles cuproptosis. 24 h treatment with 20 nM elesclomol 2 µM CuCl performed promote occurrence Cuproptosis. Cell proliferation, migration assays ware utilized analyze effect cells. Active caspase-3 also determined after treatment. Results significantly upregulated during The si-DNMBP-AS1 increased viability nonactivated caspase-3, promoted suppress cytotoxic dose- time-dependent manner. Exposure 10 for did not reduce or activated but DNMBP-AS1, Anymore, reversed pro-cuproptosis function lidocaine. Conclusions time- dose-dependent manner, up-regulating results study offered initial optimism that could be an adjuvant neoadjuvant fashion cancer

Language: Английский

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