Cuproptosis: molecular mechanisms, cancer prognosis, and therapeutic applications

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Янв. 22, 2025

Cuproptosis differs from other forms of cell death, such as apoptosis, necroptosis, and ferroptosis, in its unique molecular mechanisms signaling pathways. In this review, we delve into the cellular metabolic pathways copper, highlighting role copper biomolecule synthesis, mitochondrial respiration, antioxidant defense. Furthermore, elucidate relationship between cuproptosis-related genes (CRGs) cancer prognosis, analyzing their expression patterns across various tumor types impact on patient outcomes. Our review also uncovers potential therapeutic applications chelators, ionophores, copper-based nanomaterials oncology. addition, discuss emerging cuproptosis remodeling microenvironment, enhancing immune infiltration, converting "cold tumors" "hot that respond better to immunotherapy. short, underscores pivotal importance biology highlights translational a novel target.

Язык: Английский

---

Cuproptosis-Related MiR-21-5p/FDX1 Axis in Clear Cell Renal Cell Carcinoma and Its Potential Impact on Tumor Microenvironment

Cells, Год журнала: 2022, Номер 12(1), С. 173 - 173

Опубликована: Дек. 31, 2022

As a newly identified type of programmed cell death, cuproptosis may have an impact on cancer development, including clear renal carcinoma (ccRCC). Herein, we first noticed that the expression levels regulators exhibited tight correlation with clinicopathological characteristics ccRCC. The cuproptosis-sensitive sub-type (CSS), classified via consensus clustering analysis, harbored higher overall survival rate compared to cuproptosis-resistant (CRS), which resulted from differential infiltration immune cells. FDX1, master regulator, was experimentally determined as tumor suppressor in ccRCC cells by suppressing growth and invasion ACHN OSRC-2 cuproptosis-dependent -independent manner. results IHC staining also demonstrated FDX1 negatively correlated initiation progression. Furthermore, miR-21-5p/FDX1 axis verified miR-21-5p directly binds 3′-UTR mediate its degradation. Consequently, inhibitor suppressed cells, could be compensated knockdown, reinforcing functional linkage between Finally, evaluated microenvironment under noted this strongly associated such CD4+ T Treg macrophages, suggesting signaling alter microenvironmental components drive Overall, study constructed analyzed potential microenvironment, providing valuable insights improve current management.

Язык: Английский

---

Melanoma biology and treatment: a review of novel regulated cell death-based approaches

Cancer Cell International, Год журнала: 2024, Номер 24(1)

Опубликована: Фев. 9, 2024

Abstract The incidence of melanoma, the most lethal form skin cancer, has increased due to ultraviolet exposure. treatment advanced particularly metastatic cases, remains challenging with poor outcomes. Targeted therapies involving BRAF/MEK inhibitors and immunotherapy based on anti-PD1/anti-CTLA4 antibodies have achieved long-term survival rates approximately 50% for patients melanoma. However, therapy resistance inadequate response continue hinder further breakthroughs in treatments that increase rates. This review provides an introduction molecular-level pathogenesis melanoma offers overview current options their limitations. Cells can die by either accidental or regulated cell death (RCD). RCD is orderly controlled a variety macromolecules maintain stability internal environment. Since uncontrolled proliferation tumor cells requires evasion programs, inducing may be strategy. summarizes studies various types nonapoptotic RCDs, such as autophagy-dependent death, necroptosis, ferroptosis, pyroptosis, recently discovered cuproptosis, context relationships between these RCDs are examined, interplay targeted discussed. Given findings demonstrating different stimuli associated induction shows promise integral component strategies

Язык: Английский

---

Integrated analysis of single-cell RNA-seq and chipset data unravels PANoptosis-related genes in sepsis

Frontiers in Immunology, Год журнала: 2024, Номер 14

Опубликована: Янв. 3, 2024

Background The poor prognosis of sepsis warrants the investigation biomarkers for predicting outcome. Several studies have indicated that PANoptosis exerts a critical role in tumor initiation and development. Nevertheless, has not been fully elucidated. Methods We obtained Sepsis samples scRNA-seq data from GEO database. PANoptosis-related genes were subjected to consensus clustering functional enrichment analysis, followed by identification differentially expressed calculation score. A PANoptosis-based prognostic model was developed. In vitro experiments performed verify distinct genes. An external dataset used cellular localization. Results Unsupervised analysis using 16 identified three subtypes sepsis. Kaplan-Meier showed significant differences patient survival among subtypes, with different immune infiltration levels. Differential 48 DEGs. Boruta algorithm PCA DEGs as signature developed PANscore based on these genes, which can distinguish clinical characteristics may serve potential biomarker. Single-cell sequencing six cell types, high relatively B cells, low CD16+ CD14+ monocytes Megakaryocyte progenitors. ZBP1, XAF1, IFI44L, SOCS1, PARP14 higher cells PANscore. Conclusion machine learning profiling related subgroups features

Язык: Английский

---

Copper in melanoma: at the crossroad of protumorigenic and anticancer roles

Redox Biology, Год журнала: 2025, Номер 81, С. 103552 - 103552

Опубликована: Фев. 15, 2025

Язык: Английский

---

Cancer‐Associated Fibroblast Signature Can Predict Prognosis and Therapeutic Responses in Skin Cutaneous Melanoma

Pigment Cell & Melanoma Research, Год журнала: 2025, Номер 38(2)

Опубликована: Фев. 26, 2025

ABSTRACT Skin cutaneous melanoma (SKCM) is a lethal skin cancer with poor prognosis and limited response to immunotherapy. Cancer‐associated fibroblasts (CAFs) are key contributors tumor progression, therapy resistance, immunosuppression. In this study, mRNA sequencing clinical data from SKCM samples were obtained The Cancer Genome Atlas (TCGA) Gene Expression Omnibus (GEO) databases evaluate the prognostic significance, therapeutic implications, potential for enhancing immunotherapy through targeting CAFs in SKCM. A CAF‐related risk model comprising nine genes was developed, revealing that patients classified as low‐risk exhibited superior survival outcomes increased sensitivity Spearman correlation analysis identified significant associations between score 40 drugs, well resistance 17 drugs. Additionally, categorized into three distinct subgroups SKCM, antigen‐presenting (apCAFs) notably suppressing infiltration of anti‐tumor immune cells strongly correlating prognosis. summary, offers robust tool capable predicting both sensitivity. Moreover, pivotal role apCAFs within microenvironment suggests these may enhance efficacy

Язык: Английский

---

CDKN2A, a key gene in copper-induced cell death model, influencing melanoma invasion and apoptosis

Discover Oncology, Год журнала: 2025, Номер 16(1)

Опубликована: Фев. 27, 2025

Skin cutaneous melanoma (SKCM) is one of the most lethal cancers translating into 75% skin cancer-related deaths. Despite advances in SKCM management and treatment strategies, overall survival patients remains unsatisfactory due to metastatic properties as well absence effective prognostic biomarkers. Recent studies have shown that overload copper renders accumulation mitochondrial proteins fuels a form cell death at odds with known mechanisms hinged on respiration, so-called cuproptosis. However, exact role cuproptosis development progression unknown, painting clear picture its functions fraught challenges. A more systematic investigation justified. In this study, we were posed dissect clout latent regulatory cuproptosis-related genes (CRGs) reining progression. Also, identified three CRGs stood out used construct model, which could be employed predict prognosis SKCM. Finally, through pan-cancer analysis, found four key play multiple tumors, suggesting may impact tumor level. Taken together, these findings not only contribute strategies but also provide clues for decision-making.

Язык: Английский

---

Cell Death Modalities in Therapy of Melanoma

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(8), С. 3475 - 3475

Опубликована: Апрель 8, 2025

Melanoma, one of the most lethal cancers, demands urgent and effective treatment strategies. However, a successful therapeutic approach requires precise understanding mechanisms underlying melanoma initiation progression. This review provides an overview pathogenesis, identifies current pathogenic factors contributing to mortality, explores targeted therapy checkpoint inhibitor therapy. Furthermore, we examine classification corresponding therapies, along with advancements in various cell death for treatment. We also discuss status some drawbacks encountered during research stages such as resistance metastasis.

Язык: Английский

---

Role of hippo pathway and cuproptosis-related genes in immune infiltration and prognosis of skin cutaneous melanoma

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Март 7, 2024

Melanoma is the most lethal type of skin cancer with an increasing incidence. Cuproptosis recently identified copper-dependent form cell death that relies on mitochondrial respiration. The hippocampal (Hippo) pathway functions as a tumor suppressor by regulating Yes-associated protein/transcriptional coactivator PDZ-binding motif (YAP/TAZ) activity. However, its role in cuproptosis remains unknown. In addition, correlation cuproptosis-related genes and Hippo pathway-related prognosis warrants further investigation. present study, we explored melanoma through analysis data from public database experimental verification. We found eight were downregulated exhibited predictive value for prognosis. There was significant positive between cutaneous melanoma. YAP1 expression positively correlated ferredoxin 1 (FDX1) GSE68599 dataset A2058 cells. Moreover, negatively M2 macrophages regulatory T infiltration, respectively. conclusion, study demonstrated prognostic (particularly YAP1) melanoma, revealing immune infiltration. Thus, findings may provide new clues assessment patients target immunotherapy this disease.

Язык: Английский

---

Cuproptosis-related DNA methylation signature predict prognosis and immune microenvironment in cutaneous melanoma

Discover Oncology, Год журнала: 2024, Номер 15(1)

Опубликована: Июнь 14, 2024

Abstract The prognosis for Cutaneous Melanoma (CM), a skin malignant tumor that is extremely aggressive, not good. A recently identified type of controlled cell death intimately related to immunotherapy and the development cancer called cuproptosis. Using Cancer Genome Atlas (TCGA) Gene Expression Omnibus (GEO) database, we developed validated DNA-methylation located in cuproptosis death-related gene prognostic signature (CRG-located signature) predict CM’s prognosis. Kaplan–Meier analysis our TCGA GEO cohorts showed high-risk patients had shorter overall survival. area under curve (AUC) cohort was 0.742, while it 0.733, according receiver operating characteristic (ROC) analysis. Furthermore, this discovered as an independent indicator over CM based on Cox-regression Immunogenomic profiling indicated majority immune-checkpoints got opposite relationship with signature, group at low risk higher immunophenoscore. Several immune pathways were enriched, functional enrichment In conclusion, methylation established confirmed. Because its close landscape, may help clinicians make more accurate individualized choices regarding therapy.

Язык: Английский

---