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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Cuproptosis related genes associated with Jab1 shapes tumor microenvironment and pharmacological profile in nasopharyngeal carcinoma

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

Published: Dec. 23, 2022

Nasopharyngeal carcinoma (NPC) is the most common subcategory of head and neck squamous cell (HNSCC). This study focused on roles cuproptosis related genes Jab1 in tumor microenvironment NPC HNSCC.Differential expression analysis enriched region (PanCK-expressing) immune (CD45-expressing) were performed by packages R software. Survival was using survival survminer packages. Corrplot package used for correlation analysis. ConsensusClusterPlus cluster clustering among different regions NPC, functional enrichment GSVA, GSEABase, clusterProfiler, org.Hs.eg.db enrichplot The pRRophetic to predict drug sensitivity HNSCC.Relationships exist between microenvironment. differed region. AKT inhibitor VIII, Doxorubicin, Bleomycin Etoposide showed higher than cell. In high group, ATP7A, DBT, DLD LIAS associated with better prognosis HNSCC patients. contrast, low these worse patients.Prognostic provided a basis targeted therapy development.

Language: Английский

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Cuproptosis-associated CDKN2A is targeted by plicamycin to regulate the microenvironment in patients with head and neck squamous cell carcinoma

Frontiers in Genetics, Journal Year: 2023, Volume and Issue: 13

Published: Jan. 9, 2023

Head and neck squamous cell carcinoma (HNSCC), the most common malignancy of head neck, has an overall 5-year survival rate <50%. Genes associated with cuproptosis, a newly identified copper-dependent form death, are aberrantly expressed in various tumours. However, their role HNSCC remains unknown. In this study, bioinformatic analysis revealed that cuproptosis-related gene CDKN2A was correlated malignant behaviour HNSCC. Kaplan-Meier (KM) curves showed patients high expression had better prognosis. Multiomic may be cycle immune infiltration tumour microenvironment is important for maintaining systemic homeostasis body. Furthermore, molecular docking dynamics simulations suggested strong binding between plicamycin CDKN2A. And inhibits progression cellular assays. conclusion, study elucidated potential mechanism action cuproptosis-associated targets to improve prognosis patients.

Language: Английский

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Construction and significance of a breast cancer prognostic model based on cuproptosis-related genotyping and lncRNAs

Journal of the Formosan Medical Association, Journal Year: 2024, Volume and Issue: unknown

Published: May 1, 2024

/Purpose: Cuproptosis may play a significant role in breast cancer (BC). We aimed to investigate the prognostic impact of cuproptosis-related lncRNAs BC. Consensus clustering analysis categorized TCGA-BRCA samples into 3 clusters, followed by survival and immune analyses clusters. LASSO-COX was performed on differentially expressed BC construct model. Gene Ontology/Kyoto Encyclopedia Genes Genomes (GO/KEGG) enrichment, immune, drug prediction were high-risk low-risk groups. Cell experiments conducted analyze results two (AC104211.1 LINC01863). Significant differences observed outcomes infiltration levels among three clusters (p < 0.05). The validation model showed between groups both training sets Differential mRNAs significantly enriched Neuroactive ligand-receptor interaction cAMP signaling pathway. Additionally, found levels, human leukocyte antigen (HLA) expression, Immunophenoscore (IPS) scores, Tumor Immune Dysfunction Exclusion (TIDE) scores Drug corresponding cell experimental that Trametinib, 5-fluorouracil, AICAR inhibited viability MCF-7 cells AC104211.1 LINC01863 proliferation cells. risk-scoring obtained this study serve as robust biomarker, potentially aiding clinical decision-making for patients.

Language: Английский

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Stem cell status and prognostic applications of cuproptosis-associated lncRNAs in acute myeloid leukemia

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 12

Published: Jan. 14, 2025

Acute myeloid leukemia (AML), a highly heterogeneous hematological malignancy, remains major challenge in adult oncology. Stem cell research has highlighted the crucial role of long noncoding RNA (lncRNA) regulating cellular differentiation and self-renewal processes, which are pivotal AML pathogenesis therapy resistance. This study explores relationship between cuproptosis-related lncRNAs prognosis, providing novel insights into their impact on hematopoietic stem progenitor cells. We collected clinical information from 214 patients our center analyzed association granulocyte recovery after chemotherapy, cuproptosis, prognosis. Additionally, we developed prognostic model-the cuproptosis-associated model (CRLPM)-y analyzing data The Cancer Genome Atlas (TCGA). Patients were stratified high- low-risk groups based CRLPM, revealing significant survival differences. High-risk demonstrated lower sensitivity to chemotherapeutic agents such as Axitinib, GSK429286A, Navitoclax, ZM-447439, underscoring need for alternative therapeutic strategies. CRLPM offers promising framework integrating cell-focused approaches personalized treatment regimens, paving way precision medicine management.

Language: Английский

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Bioinformatic analysis and experimental validation of cuproptosis-related LncRNA as a novel biomarker for prognosis and immunotherapy of oral squamous cell carcinoma

Hereditas, Journal Year: 2024, Volume and Issue: 161(1)

Published: Feb. 27, 2024

Abstract Background The novel form of regulatory cell death, cuproptosis, is characterized by proteotoxicity, which ultimately leads to death. Its targeting has emerged as a promising therapeutic approach for oral squamous carcinoma (OSCC). Long noncoding RNAs (lncRNAs) participate in epigenetic regulation and have been linked the progression, prognosis, treatment OSCC. Thus, this study aimed identify new cuproptosis-related lncRNAs (CRLs), establish predictive models clinical immune response, drug sensitivity, provide insights into escape tumor resistance. Methods present screened eight CRLs (THAP9-AS1, STARD4-AS1, WDFY3-AS2, LINC00847, CDKN2A-DT, AL132800.1, GCC2-AS1, AC005746.1) using Lasso Cox regression analysis develop an eight-CRL prognostic model. Patients were categorized high- low-risk groups risk scores. To evaluate ability model, Kaplan-Meier analysis, ROC curves, nomograms employed. Furthermore, investigated differences function anticancer sensitivity between groups. validate expression OSCC lines subjected quantitative real-time fluorescence PCR (qRT-PCR). Results results showed that high-risk group had shorter overall survival (OS) time patients. demonstrated score was independent factor poor prognosis. validity model confirmed curve nomogram developed predict prognosis patients with high TMB poorer responded better immunotherapy than those group. Additionally, scores significantly associated Finally, findings qRT-PCR supported reliability proposed Conclusion identified established 8-CRL represents pathway lncRNA cuproptosis This provides guidance offers insight

Language: Английский

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Clinical significance and integrative analysis of the cuproptosis-associated genes in head and neck squamous cell carcinoma

Aging, Journal Year: 2023, Volume and Issue: 15(6), P. 1964 - 1976

Published: March 20, 2023

Aging | doi:10.18632/aging.204579. Qiu Peng, Xianjie Jiang, Shiming Tan, Xuemeng Xu, Longzheng Xia, Nayiyuan Wu, Jinguan Lin, Linda Oyang, Yanyan Tang, Mingjing Min Su, Xia Luo, Yaqian Han, Qianjin Liao, Yujuan Zhou

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The role of novel programmed cell death in head and neck squamous cell carcinoma: from mechanisms to potential therapies

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

Published: Sept. 25, 2023

Head and neck squamous cell carcinoma (HNSCC) is a common oral cancer with poor prognosis for which no targeted therapeutic strategies are currently available. Accumulating evidence has demonstrated that programmed death (PCD) essential in the development of HNSCC as second messenger. PCD can be categorized into numerous different subroutines: addition to two well-known types apoptosis autophagy, novel forms (e.g., necroptosis, pyroptosis, ferroptosis, NETosis) also serve key alternatives tumorigenesis. Cancer cells not able avoid all simultaneously, since subroutines follow regulatory pathways. Herein, we summarize roles tumorigenesis present our interpretations molecular mechanisms view further potential therapies.

Language: Английский

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Prognostic prediction of head and neck squamous cell carcinoma: Construction of cuproptosis‐related long non‐codingRNAsignature

Journal of Clinical Laboratory Analysis, Journal Year: 2022, Volume and Issue: 36(11)

Published: Oct. 3, 2022

Recently, a new type of programmed cell death, cuproptosis, has been identified to play important role in the progression tumors. We constructed cuproptosis-related long non-coding RNA (lncRNA) signature predict prognostic significance for head and neck squamous carcinoma (HNSCC).The risk model was developed based on differentially expressed lncRNAs associated with cuproptosis. Principal component analysis used assess validity. The Kaplan-Meier curves were analyzed compare overall survival (OS), disease-specific (DSS), progression-free (PFS) values. multivariate univariate Cox regression analyses evaluate efficiency. Furthermore, functional enrichment, immune infiltration, tumor mutation burden (TMB), sensitivity toward chemotherapy also explored.Six (AL109936.2, CDKN2A-DT, AC090587.1, KLF3-AS1, AL133395.1, LINC01063) construct independent predictor HNSCC. area under curve C-index values obtained using higher than corresponding clinical factors. Analysis indicated that OS, PFS, DSS time recorded patients low-risk group belonging high-risk group. By enrichment analysis, we observed genes enriched response tumor-associated pathways. characterized by score exhibited better infiltration other individuals chemotherapeutic agents (cisplatin, docetaxel, paclitaxel) those group.A lncRNA-based functioned as an prognosis HNSCC constructed. chemosensitivity individual can be potentially predicted this signature.

Language: Английский

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The role of cuproptosis-related genes in pan-cancer and the development of cuproptosis-related risk model in colon adenocarcinoma

Heliyon, Journal Year: 2024, Volume and Issue: 10(14), P. e34011 - e34011

Published: July 1, 2024

Cancer is widely regarded as a leading cause of death in humans, with colon adenocarcinoma (COAD) ranking among the most prevalent types. Cuproptosis novel form cell mediated by protein lipoylation. Cuproptosis-related genes (CRGs) participate tumourigenesis and development. Their role pan-cancer COAD require further investigation. This study comprehensively evaluated relationship CRGs, pan-cancer, COAD. Our research revealed differential expression CRGs cuproptosis potential index (CPI) between normal tumour tissues, explored correlation or CPI prognosis, immune infiltration, tumor mutant burden(TMB), microsatellite instability (MSI), drug sensitivity pan-cancer. Gene set enrichment analysis (GSEA) that oxidative phosphorylation fatty acid metabolism pathways were significantly enriched high group tumours. FDX1 CDKN2A chosen for exploration, we found an independent association TMB, MSI Furthermore, prognostic risk model based on was built, correlations score immune-related characteristics, analysed. then divided into three subtypes using cluster analysis, differences CPI, determined. Due to level LIPT1 notably positive related score, cytological identification carried out identify proliferation migration cancer cells. In summary, can be used biomarkers predict infiltration levels patients addition, could more accurately prognosis better guide direction clinical medication. Thus, FDX1, CDKN2A, may serve prospective new targets therapy.

Language: Английский

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