Copper homeostasis and copper-induced cell death： Novel targeting for intervention in the pathogenesis of vascular aging DOI Open Access
Zhuoying Chen, Yuanyuan Li, Xiangjie Liu

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 169, P. 115839 - 115839

Published: Nov. 16, 2023

Copper-induced cell death, also known as cuproptosis, is distinct from other types of death such apoptosis, necrosis, and ferroptosis. It can trigger the accumulation lethal reactive oxygen species, leading to onset progression aging. The significant increases in copper ion levels aging populations confirm a close relationship between homeostasis vascular On hand, closely related occurrence various cardiovascular diseases throughout process. However, specific causes are not clear, different living environments stress patterns lead individualized By exploring correlations copper-induced aging, we gain novel perspective on pathogenesis enhance prognosis atherosclerosis. This article aims provide comprehensive review impacts including their effects endothelial cells, smooth muscle oxidative stress, ferroptosis, intestinal flora, factors. Furthermore, intend discuss potential strategies involving cuproptosis new insights for copper-related

Language: Английский

Pan-cancer analyses confirmed the cuproptosis-related gene FDX1 as an immunotherapy predictor and prognostic biomarker DOI Creative Commons
Chi Zhang,

Yuanxiao Zeng,

Xiuchen Guo

et al.

Frontiers in Genetics, Journal Year: 2022, Volume and Issue: 13

Published: Aug. 5, 2022

Background: The latest research identified cuproptosis as an entirely new mechanism of cell death. However, a key regulator in copper-induced death, the prognostic and immunotherapeutic value FDX1 pan-cancer remains unclear. Methods: Data from UCSC Xena, GEPIA, CPTAC were analyzed to conduct inquiry into overall differential expression across multiple cancer types. GBM, LUAD HCC lines well their control was verified by RT-QPCR. survival prognosis, clinical features, genetic changes also evaluated. Finally, relationship between immunotherapy response further explored through Gene Set Enrichment Analysis enrichment analysis, tumor microenvironment, immune infiltration, gene co-expression drug sensitivity analysis. Results: transcription protein significantly reduced most types had for certain patients such ACC, KIRC, HNSC, THCA LGG. In some types, markedly correlated with characteristics, TMB, MSI, antitumor susceptibility or resistance different tumors. set analysis showed that associated immune-related pathways. Moreover, level confirmed be strongly checkpoint genes, regulatory genes extent. Conclusion: This study comprehensively potential marker pan-cancer, providing direction evidence therapy.

Language: Английский

Citations

69
A Cuproptosis Activation Scoring model predicts neoplasm-immunity interactions and personalized treatments in glioma DOI Creative Commons
Bo Chen,

Xiaoxi Zhou,

Liting Yang

et al.

Computers in Biology and Medicine, Journal Year: 2022, Volume and Issue: 148, P. 105924 - 105924

Published: Aug. 8, 2022

Gliomas are malignant tumors in the central nervous system. Cuproptosis is a newly discovered cell death mechanism targeting lipoylated tricarboxylic acid cycle proteins. Previous studies have found that cuproptosis participates tumor progression, but its role gliomas still elusive. Here, we systematically explored bulk-tumor and single-cell transcriptome data to reveal gliomas. The activity score (CuAS) was constructed based on cuproptosis-related genes, machine learning techniques validated stability. High CuAS were more likely poor prognosis an aggressive mesenchymal (MES) subtype. Subsequently, SCENIC algorithm predicted 20 CuAS-related transcription factors (TFs) Function enrichment microenvironment analyses associated with immune infiltration. Accordingly, intercellular communications between neoplasm immunity by R package "Cellchat". Five signaling pathways 8 ligand-receptor pairs including ICAM1, ITGAX, ITGB2, ANXA1-FRR1, like, identified suggest how connected neoplastic cells. Critically, 13 potential drugs high CuAs according CTRP PRISM databases, oligomycin A, dihydroartemisinin, others. Taken together, involved glioma aggressiveness, neoplasm-immune interactions, may be used assist drug selection.

Language: Английский

Citations

55
Photothermal therapy-mediated autophagy in breast cancer treatment: Progress and trends DOI
Jamileh Kadkhoda, Ali Tarighatnia, Mohammad Reza Tohidkia

et al.

Life Sciences, Journal Year: 2022, Volume and Issue: 298, P. 120499 - 120499

Published: March 25, 2022

Language: Английский

Citations

54
A novel cuproptosis-related prognostic lncRNA signature and lncRNA MIR31HG/miR-193a-3p/TNFRSF21 regulatory axis in lung adenocarcinoma DOI Creative Commons

Xiaocong Mo,

Di Hu,

Pingshan Yang

et al.

Frontiers in Oncology, Journal Year: 2022, Volume and Issue: 12

Published: July 22, 2022

Lung adenocarcinoma (LUAD) remains the most common subtype of lung malignancy. Cuproptosis is a newly identified cell death which could regulate tumor proliferation and progression. Long non-coding RNAs (lncRNAs) are key molecules potential biomarkers for diagnosing treating various diseases. However, effects cuproptosis-related lncRNAs on LUAD still unclear. In our study, 7 were selected to establish prognostic model using univariate Cox regression analysis, LASSO algorithm, multivariate analysis. Furthermore, we evaluated AC008764.2, AL022323.1, ELN-AS1, LINC00578, as protective lncRNAs, while AL031667.3, AL606489.1, MIR31HG risk lncRNAs. The score calculated by proved be an effective independent factor compared with other clinical features analyses [univariate analysis: hazard ratio (HR) = 1.065, 95% confidence interval (CI) 1.043-1.087, P < 0.001; HR 1.067, CI 1.044-1.091, 0.001]. addition, both (ROC nomogram) used corroborate accuracy reliability this signature. correlation between immune microenvironment was elucidated, where cells 8 immune-correlated pathways found differentially expressed two groups. results also verified ceRNA lncRNA MIR31HG/miR-193a-3p/TNFRSF21 regulatory axis bioinformatics tools. highly in specimens some lines. Inhibition clearly reduced proliferation, migration, invasion cells. showed oncogenic via sponging miR-193a-3p tended positively TNFRSF21 expression. word, acts oncogene targeting modulate TNFRSF21, may beneficial gene therapy LUAD.

Language: Английский

Citations

50
The Molecular Mechanisms of Defective Copper Metabolism in Diabetic Cardiomyopathy DOI Creative Commons
Xiangning Cui, Yan Wang, Han Liu

et al.

Oxidative Medicine and Cellular Longevity, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 16

Published: Oct. 4, 2022

Copper is an essential trace metal element that significantly affects human physiology and pathology by regulating various important biological processes, including mitochondrial oxidative phosphorylation, connective tissue crosslinking, antioxidant defense. level has been proved to be closely related the morbidity mortality of cardiovascular diseases such as atherosclerosis, heart failure, diabetic cardiomyopathy (DCM). deficiency can induce cardiac hypertrophy aggravate cardiomyopathy, while copper excess mediate types cell death, autophagy, apoptosis, cuproptosis, pyroptosis, fibrosis. Both lead redox imbalance, activate inflammatory response, cardiomyopathy. This defective metabolism suggests a specific metabolic pattern in diabetes role pathogenesis progression DCM. review aimed at providing timely summary effects homeostasis on DCM discussing potential underlying molecular mechanisms.

Language: Английский

Citations

44
Cuproptosis predicts the risk and clinical outcomes of lung adenocarcinoma DOI Creative Commons
Qin Hu, Runtian Wang,

Huiyun Ma

et al.

Frontiers in Oncology, Journal Year: 2022, Volume and Issue: 12

Published: Aug. 8, 2022

Copper is an essential microelement for the body and a necessary coregulator enzymatic reactions, yet unbalanced copper level promotes reactive oxidation cytotoxicity, which ultimately induces cell death. Several small molecules targeting copper-induced death have been investigated, few showed promising therapeutic effects in clinical trials. In March 2022, Science first introduced concept mechanisms of cuproptosis, suggesting that targets tricarboxylic acid (TCA) cycle via protein lipoylation. Does this novel form take part tumorigenesis or tumor progression? Is cuproptosis related to outcomes diseases? there cuproptosis-related panel practice cancer treatment? Herein, based on 942 samples lung adenocarcinoma (LUAD), we analyzed gene set existence predictive value disease diagnosis treatment. We screened out identified “cupLA” indicates risk LUAD occurrence, clinicopathological features patients, could guide clinicians refine subtypes make treatment choices.

Language: Английский

Citations

43
Copper-instigated modulatory cell mortality mechanisms and progress in oncological treatment investigations DOI Creative Commons
Lei Gao, Anqi Zhang

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

Published: Aug. 2, 2023

Copper, a transition metal, serves as an essential co-factor in numerous enzymatic active sites and constitutes vital trace element the human body, participating crucial life-sustaining activities such energy metabolism, antioxidation, coagulation, neurotransmitter synthesis, iron tetramer deposition. Maintaining equilibrium of copper ions within biological systems is paramount importance prevention atherosclerosis associated cardiovascular diseases. Copper induces cellular demise through diverse mechanisms, encompassing reactive oxygen species responses, apoptosis, necrosis, pyroptosis, mitochondrial dysfunction. Recent research has identified dubbed novel regulatory cell death modality—”cuprotosis”—wherein bind to acylated proteins tricarboxylic acid cycle respiration, resulting protein aggregation, subsequent downregulation iron-sulfur cluster expression, induction proteotoxic stress, eventual death. Scholars have synthesized complexes by combining with various ligands, exploring their significance applications cancer therapy. This review comprehensively examines multiple pathways copper-induced death, current status treatment.

Language: Английский

Citations

40
The expression of cuproptosis-related genes in hepatocellular carcinoma and their relationships with prognosis DOI Creative Commons
Xueying Zhao, Jin Chen,

Shangqi Yin

et al.

Frontiers in Oncology, Journal Year: 2022, Volume and Issue: 12

Published: Oct. 14, 2022

The mechanism of cuproptosis has recently been reported in lipoylated proteins the tricarboxylic acid (TCA) cycle. Besides, role copper was previously recognized cancer progression. We evaluated prognostic value cuproptosis-related gene expression hepatocellular carcinoma (HCC). Remarkable genes were selected both differential analysis and Kaplan-Meier survival from ninety-six using Cancer Genome Atlas (TCGA) database. relationships between clinical characteristics performed with Wilcoxon signed-rank test, Kruskal-Wallis logistic regression. Clinicopathologic factors correlated overall HCCs conducting univariate multivariate Cox regression analysis. Gene Expression Profiling Interactive Analysis 2 (GEPIA2) Human Protein (HPA) databases utilized to verify results. Furthermore, Set Enrichment (GSEA) identified potential key pathways that dominate HCC. Elevated ATP7A, SLC25A3, SCO2, COA6, TMEM199, ATP6AP1, LIPT1, DLAT, PDHA1, MTF1, ACP1, FDX2, NUBP2, CIAPIN1, ISCA2 NDOR1 expression, as well declined AOC1, FDX1, MT-CO1, ACO1 significantly emerged HCC tumor tissues associated poor survival. expressions screened prominently related features. GSEA many signaling (such natural killer cell mediated cytotoxicity, TCA cycle, glutathione metabolism, ATP-binding cassette (ABC) transporters, Notch pathway, ErbB metabolism xenobiotics by cytochrome p450) differentially enriched varying degrees expression. twenty might be new candidate biomarkers for

Language: Английский

Citations

38
Cuproptosis is involved in copper-induced hepatotoxicity in chickens DOI

Gaolong Zhong,

Lei Li, Yuanxu Li

et al.

The Science of The Total Environment, Journal Year: 2023, Volume and Issue: 866, P. 161458 - 161458

Published: Jan. 6, 2023

Language: Английский

Citations

37
Multifaceted Roles of Copper Ions in Anticancer Nanomedicine DOI Open Access
Siyuan Yang,

Yingnan Song,

Yanling Hu

et al.

Advanced Healthcare Materials, Journal Year: 2023, Volume and Issue: 12(23)

Published: April 7, 2023

Abstract The significantly increased copper level in tumor tissues and serum indicates the close association of ions with development, making attractive targets development novel treatment methods. advanced nanotechnology developed past decades provides great potential for therapy, among which Cu‐based nanotherapeutic systems have received greater attention. Herein, multifaceted roles cancer progression are summarized recent advances copper‐based nanostructures or nanomedicines different kinds therapies including depletion cytotoxins, copper‐ion‐based chemodynamic therapy its combination other treatments, copper‐ion‐induced ferroptosis cuproptosis activation discussed. Furthermore, perspectives further clinic translation presented by authors.

Language: Английский

Citations

35