Targeting cuproptosis for cancer therapy: Focus on the anti-tumor immune system DOI Creative Commons
Xuan Zhang, Xiaohong Han

Cancer Pathogenesis and Therapy, Journal Year: 2024, Volume and Issue: unknown

Published: July 1, 2024

Copper (Cu) is an indispensable micronutrient that maintains signaling pathways and biological homeostasis in almost all cell types; however, its excess affects the tricarboxylic acid cycle, causes accumulation of fatty acylated proteins, destabilization iron–sulfur cluster increases levels intracellular reactive oxygen species, leading to proteotoxic stress death. Cuproptosis, a form Cu-dependent death, differs from other types regulated death (RCD) was first reported Science 2022. Recently, RCD have been targeted cancer therapy. However, escape apoptosis tumor cells resistance treatment recurrence. Therefore, there urgent need study alternative mechanisms mortality. Compared normal patients, significant increase serum Cu ion has observed patients with tumors. Moreover, proliferation, angiogenesis, metastasis are associated cuproptosis. Thus, exploring related cuproptosis will provide new perspective for development anti-cancer drugs. Importantly, closely modulation anti-tumor immunity. The expression cuproptosis-related genes (CRGs) significantly correlated immune infiltration checkpoint programmed protein 1 (PD-1)/programmed death-ligand (PD-L1). Based on these findings, series drugs used tumor-targeted combination therapy or as synergists. elucidating role per stage microenvironment (TIME) helpful clarifying potential value specific cancers. In this review, we summarize based regulation concentration. two approaches may help researchers develop more therapies targeting pathways. focused effect TIME systematically discussed CRGs immunity considering CRG-related pathways, prognosis scoring system, immunotherapy, experiments bioinformatics prediction models, ideas anticancer

Language: Английский

ATP7A as a prognostic biomarker and potential therapeutic target in gastric cancer DOI

Zhongmei Shi,

Zhiyun Mao,

Ming Cui

et al.

American Journal of Translational Research, Journal Year: 2025, Volume and Issue: 17(1), P. 512 - 527

Published: Jan. 1, 2025

To investigate the roles of Cu transporter ATPase copper transporting alpha (ATP7A) in gastric cancer (GC) progression and prognosis. ATP7A expression was investigated using databases, immunohistochemistry (IHC) qPCR tumor tissues GC cell lines. Diagnostic prognostic value assessed by Receiver Operating Characteristic (ROC) Kaplan-Meier curve, respectively. The were explored protein-protein interaction (PPI), Gene Ontology (GO), Kyoto Encyclopedia Genes Genomes (KEGG) Set Enrichment Analysis (GSEA), ssGSEA algorithm Tumor Immune Estimation Resource (TIMER) databases. Subsequently, effects evaluated Cell Counting Kit-8 (CCK-8), colony formation, transwell assays. overexpression associated with a higher IHC score larger area under ROC curve (0.746). Elevated correlated shorter survival time, greater invasion depth lesions, advanced pathological stages, older age patients. Comprehensive analysis revealed that involved ion transport, transition metal homeostasis, cellular homeostasis. Additionally, linked to key signaling pathways, including Hedgehog, Wnt/β-catenin, Notch, along top 10 hub genes. Furthermore, played role immune infiltration, influencing T cells, dendritic B macrophages, neutrophils, as well checkpoints such Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA-4), Programmed Death 1 Ligand (PD-L1), T-Cell Immunoglobulin, Mucin Domain-Containing 3 (TIM-3). Experimental validation demonstrated silencing suppressed proliferation, migration, invasion. promoted acted promising target for treatment GC.

Language: Английский

Citations

0
miR-135b: A Key Role in Cancer Biology and Therapeutic Targets DOI Creative Commons

Yingchun Shao,

Shuangshuang Zhang, Yuxin Pan

et al.

Non-coding RNA Research, Journal Year: 2025, Volume and Issue: 12, P. 67 - 80

Published: Feb. 21, 2025

miR-135b, a microRNA, is consistently up-regulated in various cancer tissues and cells, promoting progression. By inhibiting one or more target genes, miR-135b regulates phenotypes such as growth, apoptosis, migration, invasion, drug resistance, angiogenesis, establishing it critical driver of Additionally, regulated by oncogenes therapeutic drugs, highlighting its complexity potential. Significant progress has been made understanding miR-135b's impact on cell behavior, promising biomarker for diagnosis prognosis, well potential future therapies. However, despite the extensive research this topic, there no comprehensive review summarizing role mechanisms across different types. This aims to provide detailed overview biological characteristics regulatory targets, upstream signaling pathways, potential, including influence chemoresistance. The also addresses key controversies surrounding research, aiming deepen role, promote transformation clinical application, theoretical foundation developing effective treatment strategies.

Language: Английский

Citations

0
MiR-135b-5p promotes cetuximab resistance in colorectal cancer by regulating FOXN3 DOI Creative Commons
Chun Peng, Xiaoqing Li, Yuhui Yao

et al.

Cancer Biology & Therapy, Journal Year: 2024, Volume and Issue: 25(1)

Published: July 5, 2024

Despite advances in targeted therapies, primary and acquired resistance make the treatment of colorectal cancer (CRC) a pressing issue to be resolved. According reports, development CRC is linked miRNA dysregulation. Multiple studies have demonstrated that miR-135b-5p has an aberrant expression level between tissues adjacent tissues. However, it unclear whether there correlation cetuximab (CTx) CRC. Use GEO database measure Additionally, RT-qPCR was applied ascertain production three human cells NCM460 cells. The capacity migrate invade examined utilizing wound-healing transwell assays, while CCK-8 assay served for evaluating cell viability, as well colony formation assays proliferation. expected target protein been investigated using western blot. Suppression could increase CTx sensitivity CTx-resistant cells, manifested by attenuation proliferation, migration, invasion ability. Mechanistic revealed regulates epithelial-to-mesenchymal transition (EMT) process Wnt/β-catenin signaling pathway through downgulating FOXN3. In short, knockdowning FOXN3 promote EMT process, simultaneously activate elevate

Language: Английский

Citations

2
Elucidating the evolving role of cuproptosis in breast cancer progression DOI Creative Commons
Zhanyong Zhu,

Keyu Zhu,

Jun Zhang

et al.

International Journal of Biological Sciences, Journal Year: 2024, Volume and Issue: 20(12), P. 4872 - 4887

Published: Jan. 1, 2024

Breast cancer (BC) persists as a highly prevalent malignancy in females, characterized by diverse molecular signatures and necessitating personalized therapeutic approaches. The equilibrium of copper within the organism is meticulously maintained through regulated absorption, distribution, elimination, underpinning not only cellular but also various essential biological functions. process cuproptosis initiated copper's interaction with lipoylases tricarboxylic acid (TCA) cycle, which triggers conglomeration lipoylated proteins diminishes integrity Fe-S clusters, culminating cell demise proteotoxic stress. In BC, aberrations are prominent represent crucial incident that contributes to disease progression. It influences BC metabolism affects critical traits such proliferation, invasiveness, resistance chemotherapy. Therapeutic strategies target have shown promising antitumor efficacy. Moreover, plethora cuproptosis-centric genes, including cuproptosis-related genes (CRGs), CRG-associated non-coding RNAs (ncRNAs), cuproptosis-associated regulators, been identified, offering potential for development risk assessment models or diagnostic signatures. this review, we provide comprehensive exposition fundamental principles cuproptosis, its influence on malignant phenotypes prognostic implications cuproptosis-based markers, substantial prospects exploiting therapy, thereby laying theoretical foundation targeted interventions domain.

Language: Английский

Citations

1
Perspectives on the potential application of microRNAs in the diagnosis and treatment of triple-negative breast cancer DOI Creative Commons
Yinan Wu,

Haitao Song,

Huifang Shi

et al.

Oncology and Translational Medicine, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 19, 2024

Abstract Triple-negative breast cancer (TNBC) is currently the most heterogeneous and aggressive type. It has a high recurrence rate, poor clinical prospects, lack of predictive markers potential treatment options. Dysregulated microRNAs (miRNAs) are involved in various cellular processes TNBC. Moreover, variations miRNA levels TNBC may act as dependable indicator for predicting effectiveness specificity treatments. Currently, application miRNAs therapy primarily preclinical stage, with focus on identifying highly specific sensitive that could offer new possibilities early diagnosis, treatment, prognostic monitoring

Language: Английский

Citations

1
Unraveling non-coding RNAs in breast cancer: mechanistic insights and therapeutic potential DOI Creative Commons
Muqtada Shaikh, Gaurav Doshi

Medical Oncology, Journal Year: 2024, Volume and Issue: 42(1)

Published: Dec. 27, 2024

Language: Английский

Citations

1
Targeting cuproptosis for cancer therapy: Focus on the anti-tumor immune system DOI Creative Commons
Xuan Zhang, Xiaohong Han

Cancer Pathogenesis and Therapy, Journal Year: 2024, Volume and Issue: unknown

Published: July 1, 2024

Copper (Cu) is an indispensable micronutrient that maintains signaling pathways and biological homeostasis in almost all cell types; however, its excess affects the tricarboxylic acid cycle, causes accumulation of fatty acylated proteins, destabilization iron–sulfur cluster increases levels intracellular reactive oxygen species, leading to proteotoxic stress death. Cuproptosis, a form Cu-dependent death, differs from other types regulated death (RCD) was first reported Science 2022. Recently, RCD have been targeted cancer therapy. However, escape apoptosis tumor cells resistance treatment recurrence. Therefore, there urgent need study alternative mechanisms mortality. Compared normal patients, significant increase serum Cu ion has observed patients with tumors. Moreover, proliferation, angiogenesis, metastasis are associated cuproptosis. Thus, exploring related cuproptosis will provide new perspective for development anti-cancer drugs. Importantly, closely modulation anti-tumor immunity. The expression cuproptosis-related genes (CRGs) significantly correlated immune infiltration checkpoint programmed protein 1 (PD-1)/programmed death-ligand (PD-L1). Based on these findings, series drugs used tumor-targeted combination therapy or as synergists. elucidating role per stage microenvironment (TIME) helpful clarifying potential value specific cancers. In this review, we summarize based regulation concentration. two approaches may help researchers develop more therapies targeting pathways. focused effect TIME systematically discussed CRGs immunity considering CRG-related pathways, prognosis scoring system, immunotherapy, experiments bioinformatics prediction models, ideas anticancer

Language: Английский

Citations

0