The potential of targeting cuproptosis in the treatment of kidney renal clear cell carcinoma

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 167, P. 115522 - 115522

Published: Sept. 25, 2023

Renal cell carcinoma (RCC) is one of the top ten malignancies and tumor-related causes death worldwide. The most common histologic subtype kidney renal clear (KIRC), accounting for approximately 75% all RCC cases. Early resection considered basic treatment patients with KIRC. However, 30% these experience recurrence post-operation. Cuproptosis, an autonomous mechanism controlling death, encompasses various molecular mechanisms multiple cellular metabolic pathways. These pathways mainly include copper signaling pathways, mitochondrial metabolism lipoic acid pathway Recent evidence shows that cuproptosis identified as a key modality plays meaningful role in tumor progression. there no published systematic review summarizes correlation between KIRC, despite fact investigations on pathogenesis KIRC have increased past years. Researchers discovered exogenous infusion accelerates dysfunction suppresses cells by inducing cuproptosis. levels tricarboxylic cycle proteins, protein, copper, ferredoxin 1 (FDX1) were dysregulated cells, prognosis high FDX1 expression better than low expression. Cuproptosis played indispensable regulation microenvironment features, progression, long-term In this review, we summarized systemic processes copper-related highlighting potential targets related to treatment.

Language: Английский

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Cuproptosis and Cuproptosis‐Based Synergistic Therapy for Cancer Treatment

ChemMedChem, Journal Year: 2024, Volume and Issue: 19(21)

Published: June 29, 2024

Abstract Copper, as an essential trace nutrient for human, plays a crucial role in numerous cellular activities, and is vital maintaining homeostasis organisms. Deviations from normal intracellular copper concentration range can disrupt the lead to cell death. Cell death process which cells lose their vitality cannot sustain metabolism, has various forms. The recently discovered cuproptosis mechanism differs previously recognized forms, triggered by accumulation. discovery of sparked interest among researchers, this been applied treatment intractable diseases, including different types cancer. However, developed cuproptosis‐based therapies have revealed certain limitations, such low immunostimulatory efficiency, poor tumor targeting, inhibition microenvironment. Therefore, researchers are devoted combining with existing cancer develop more effective synergistic therapies. This review summarizes latest research advancements cancer, focus on Finally, it provides outlook future development anti‐tumor therapy.

Language: Английский

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Integrated analyses reveal the prognostic, immunological features and mechanisms of cuproptosis critical mediator gene FDX1 in KIRC

Genes and Immunity, Journal Year: 2023, Volume and Issue: 24(4), P. 171 - 182

Published: July 10, 2023

Language: Английский

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Development and validation of cuproptosis-related lncRNAs associated with pancreatic cancer immune microenvironment based on single-cell

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

Published: Sept. 25, 2023

Background Cuproptosis, a novel mode of cell death associated with the tricarboxylic acid (TCA) cycle, is relevant to development cancer. However, impact single-cell-based Cuproptosis-associated lncRNAs on Tumor immune microenvironment (TIME) Pancreatic adenocarcinoma (PAAD) and its potential value for individualized immunotherapy has not been clarified. Methods 14 immune-related CRGs were screened by exploring interaction between differentially expressed Immune-Related Genes (IRGs) Cuproptosis-Related (CRGs) in PAAD. Next, expression amount distribution single-cell samples analyzed focusing 7-CRGs significant expressions. On one hand, MAP2K2, SOD1, VEGFA, which significantly PAAD sites normal tissues adjacent them, subjected immunohistochemical validation landscape analysis. other from these 7-CRGs, prognostic signatures established co-expression LASSO-COX regression analysis, their relevance assessed. In addition, this study only validated hub constituting signature animal model treated immunotherapy-based combination therapy using immunohistochemistry qRT-PCR but also explored targeted, chemotherapy immunotherapy. Results Based screening cohort co-expressed (CRIs), constructed 4-CRIs named CIR-score. A Nomogram integrating CIR-score clinical risk factors was basis predict survival patients. Moreover, high low-risk groups classified according median exhibited differences prognosis, landscape, bioenrichment, tumor burden, drug sensitivity. And results different mouse treatment strategies consistent trend inter-group variability sensitivity The immunotherapy, targeted therapy, better suppression effect. Conclusion CIR-score, as Cuproptosis-related TIME-specific based single cells, predicts prognosis patients provides new strategy therapy.

Language: Английский

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Evaluation the role of cuproptosis-related genes in the pathogenesis, diagnosis and molecular subtypes identification of atherosclerosis

Heliyon, Journal Year: 2023, Volume and Issue: 9(10), P. e21158 - e21158

Published: Oct. 1, 2023

BackgroundAt present, the pathogenesis of atherosclerosis has not been fully elucidated, and diagnosis treatment face great challenges. Cuproptosis is a novel cell death pattern that might be involved in development atherosclerosis. However, no research reported correlation between cuproptosis atherosclerosis.MethodsThe differential cuproptosis-related genes (CRGs) group control (A-CRGs) were discovered via expression analysis. The analysis, PPI network GO, KEGG GSEA analysis performed to investigate function A-CRGs. differences biological investigated immune infiltration GSVA. LASSO regression, nomogram machine learning models constructed predict risk. molecular subtypes clusters unsupervised cluster Subsequently, we used above methods analyze CRGs (M-CRGs) evaluate identification performance M-CRGs. Finally, verified diagnostic value for role these through validation set vitro experiments.ResultsFive A-CRGs identified they mainly related copper ion metabolism inflammatory response. based on 5 indicated had well value. A total two obtained group. There many functions clusters, such as mitochondrial outer membrane permeabilization primary immunodeficiency. In addition, 3 M-CRGs 2 clusters. Machine showed efficacy. end, results experiment confirmed genes.ConclusionThe may potential promising markers

Language: Английский

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Integrated analysis identifies cuproptosis-related gene DLAT and its competing endogenous RNAs network to predict the prognosis of pancreatic adenocarcinoma patients

Medicine, Journal Year: 2024, Volume and Issue: 103(9), P. e37322 - e37322

Published: March 1, 2024

Pancreatic adenocarcinoma (PAAD) is a highly malignant tumor with poor prognosis. However, the relationship between cuproptosis-related genes (CRGs) and its competing endogenous RNA (ceRNA) network prognosis of PAAD patients remains unclear. To investigate this relationship, we calculated difference in CRGs tissues normal using ‘limma’ R package. Additionally, employed least absolute shrinkage selection operator (LASSO) Cox regression analysis to construct prognostic signature for CRGs. Survival was performed Kaplan–Meier analysis. Furthermore, used bioinformatics tools screen CRGs-related MicroRNA (miRNA) lncRNAs. validate these findings, conducted real-time quantitative polymerase chain reaction (RT-qPCR), CCK-8, colony formation, Transwell assays assess effect DLAT vitro. Our results revealed consisting 3 (DLAT, LIAS, LIPT1). Notably, high-risk score exhibited terms overall survival (OS) ( P < .05). The receiver operating characteristic (ROC) curve evaluate showed that 1-year, 3-year, 5-year area under values predicting OS were 0.62, 0.66, 0.79, respectively. ceRNA regulatory axis LINC00857/has-miR-1179/DLAT PAAD. In vitro experiments demonstrated knockdown LINC00857 inhibited growth invasion cells. This study identified CRG-related biomarkers LIPT1) suggested involvement development Overall, provides theoretical support investigation diagnostic as well potential therapeutic targets

Language: Английский

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SEL1L3 as a link molecular between renal cell carcinoma and atherosclerosis based on bioinformatics analysis and experimental verification

Aging, Journal Year: 2023, Volume and Issue: 15(22), P. 13150 - 13162

Published: Nov. 21, 2023

Renal cancer, the most common type of kidney develops in renal tubular epithelium. Atherosclerosis aorta is primary cause atherosclerosis. However, underlying mechanisms remain unclear.The clear cell carcinoma RNA sequence profile was obtained from The Cancer Genome Atlas (TCGA) database, and atherosclerosis datasets GSE28829 GSE43292 based on GPL570 GPL6244 Gene Expression Omnibus (GEO) database. difference hub genes were identified by Limma protein-protein interaction (PPI) network R software. Functional enrichment, survival, immunoinfiltration analyses performed. role SEL1L3 ErbB/PI3K/mTOR signaling pathway, apoptosis, invasion, cycle, inflammation analyzed using western blotting.764 DEGs TCGA Kidney Clear Cell Carcinoma (KIRC) dataset. A total 344 117 screened GSE14762 GSE53757 datasets, respectively. enrichment analysis results primarily indicated transporter complex, DNA-binding transcription activator activity, morphogenesis embryonic epithelium, stem proliferation, adrenal overactivity so on. Fifteen overlapped among three datasets. PPI revealed that core gene. Survival showed lower expression levels led to a worse prognosis. Immune infiltration significantly correlated with antibody-drug conjugates (aDC), B cells, eosinophils, interstitial dendritic cells (iDC), macrophages, more.SEL1L3 plays an important may be potential link between them.

Language: Английский

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Validation of a Novel Cuproptosis–Related Prognostic Gene Marker and Differential Expression Associated with Lung Adenocarcinoma

Current Issues in Molecular Biology, Journal Year: 2023, Volume and Issue: 45(10), P. 8502 - 8518

Published: Oct. 22, 2023

Cuproptosis induction is seen as a promising alternative for immunotherapies and targeted therapies in breast cancer. The objective of this research was to examine the prognostic biological importance cuproptosis-related genes (CRGs) lung adenocarcinoma (LUAD).The following methods were used: GSE10072 dataset TCGA database analysis, differential expression analysis CRGs, function (BP) signaling pathway enrichment clinical construction signature RNA modified miRNA CRGs LUAD, immunoinfiltration immunohistochemical staining DβH, UBE2D3, SOD1, UBE2D1 LOXL2.AOC1, ATOX1, CCL8, CCS, COX11, CP, LOXL2, MAP2K2, PDK1, SCO2, UBE2D1, UBE2D3 VEGFA showed significantly higher expression, while ATP7B, PDE3B, SLC31A2, UBE2D2, UBE2D4 ULK2 lower LUAD tissues than normal tissues. We also found that ATP7B (4%), AOC1 (3%) PDE3B (2%), DβH CP (1%), PDK1 LOXL2 (1%) mutation frequencies. univariate Cox used identify have value. It identified 21 significant value, containing LOXL2. Patients with up-expression longer survival time patients down-expression time. hsa-miR-29c-3p, hsa-miR-29a-3p, hsa-miR-181c-5p, hsa-miR-1245a, etc., play an important role regulatory network, miR-29a, miR-29c miR-181c high longer, miR-1245a low longer. performed relationships between immune infiltration including B cells, CD8+ T CD4+ macrophages, neutrophils DCs.DβH, are potential candidates implicated can be further explored their application diagnostic, prognostic, therapeutic biomarkers LUAD.

Language: Английский

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Identification of the cuproptosis-related ceRNA network and risk model in acute ischemic stroke by integrated bioinformatics analysis

Egyptian Journal of Medical Human Genetics, Journal Year: 2023, Volume and Issue: 24(1)

Published: Nov. 29, 2023

Abstract Background Acute ischemic stroke (AIS) is one of the leading contributors to death and disability in adults. And cuproptosis a novel type cell death. Yet, its role AIS still unknown. Methods The mRNA, miRNA, circRNA expression data were downloaded from Gene Expression Omnibus database. We explored differentially expressed circRNAs (DEcircRNAs), microRNAs (DEmiRNAs), cuproptosis-related genes (DECuRGs) after AIS. With target prediction tools, we constructed competitive endogenous RNA (ceRNA) network mediated by Afterward, functional enrichment analysis, cytoHubba plugin, protein–protein interaction, weighted gene co-expression unsupervised clustering analysis performed determine critical relevant pathways. Machine learning techniques used identify optimal risk model. CIBERSORT was applied explore immune-infiltrating characteristics samples. Finally, two independent datasets employed verify predictive value Results Altogether, 26 DECuRGs identified this study. Enrichment revealed that they participated reactive oxygen metabolism, inflammatory responses, corresponding biological processes. Of DECuRGs, MTF1 UBE2D2 included ceRNA network, comprising three circRNA-miRNA miRNA-mRNA interaction pairs. Hub determined hub regulatory axis process cuproptosis, namely, - miR-765 circ_0040760/0068531 . finally 5-gene model ( C10orf32 , NUCB1 AX748267 MRPL28 PPP1R15A ) multiple analyses, which validated (AUC = 0.958 0.668). Besides, significant differences immune infiltration observed between patients normal controls. levels neutrophils correlated with most DECuRGs. study also associated microenvironment patients. Conclusion findings might be key nodes, including axes, exert roles provided new insights into early diagnosis treatment

Language: Английский

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Integrated bioinformatics and experiment revealed that cuproptosis is the potential common pathogenesis of three kinds of primary cardiomyopathy

Aging, Journal Year: 2023, Volume and Issue: 15(23), P. 14210 - 14241

Published: Dec. 11, 2023

Cuproptosis is a recently reported new mode of programmed cell death which might be potential co-pathogenesis three kinds primary cardiomyopathy. However, no investigation has clear relevance between cardiomyopathy and cuproptosis. In this study, the differential cuproptosis-related genes (CRGs) shared by were identified in training sets. As result, four CRGs acquired they mainly related to biological processes such as immuno-inflammatory response through analysis, correlation GSEA, GSVA immune infiltration analysis. Then, key (K-CRGs) with high diagnostic value LASSO regression. The results nomogram, machine learning, ROC calibration curve decision indicated that K-CRGs exhibited outstanding performance diagnosis After that, each disease, two molecular subtypes clusters distinguished. There many differences different associated immunoinflammation had excellent subtype identification efficacy. Eventually, from validation datasets vitro experiments verified role cardiomyopathy, cardiomyopathic pathogenesis conclusion, study found cuproptosis common promising biomarkers for

Language: Английский

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