lncRNAs as prognostic markers and therapeutic targets in cuproptosis-mediated cancer

Clinical and Experimental Medicine, Journal Year: 2024, Volume and Issue: 24(1)

Published: Sept. 26, 2024

Abstract Long non-coding RNAs (lncRNAs) have emerged as crucial regulators in various cellular processes, including cancer progression and stress response. Recent studies demonstrated that copper accumulation induces a unique form of cell death known cuproptosis, with lncRNAs playing key role regulating cuproptosis-associated pathways. These may trigger cell-specific responses to stress, presenting new opportunities prognostic markers therapeutic targets. This paper delves into the cuproptosis-mediated cancer, underscoring their potential biomarkers targets for innovative strategies. A thorough review scientific literature was conducted, utilizing databases such PubMed, Google Scholar, ScienceDirect, search terms like 'lncRNAs,' 'cuproptosis,' 'cancer.' Studies were selected based on relevance lncRNA regulation cuproptosis pathways implications prognosis treatment. The highlights significant contribution cuproptosis-related genes pathways, impacting metabolism, mitochondrial responses, apoptotic signaling. Specific are breast, lung, liver, ovarian, pancreatic, gastric cancers. objective this article is explore cancers mediated by cuproptosis.

Language: Английский

---

An exosome-derived lncRNA signature identified by machine learning associated with prognosis and biomarkers for immunotherapy in ovarian cancer

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 9, 2024

Background Ovarian cancer (OC) has the highest mortality rate among gynecological malignancies. Current treatment options are limited and ineffective, prompting discovery of reliable biomarkers. Exosome lncRNAs, carrying genetic information, promising new markers. Previous studies only focused on exosome-related genes employed Lasso algorithm to construct prediction models, which not robust. Methods 420 OC patients from TCGA datasets were divided into training validation datasets. The GSE102037 dataset was used for external validation. LncRNAs associated with selected using Pearson analysis. Univariate COX regression analysis filter prognosis-related lncRNAs. overlapping lncRNAs identified as candidate machine learning. Based 10 learning algorithms 117 combinations, optimal predictor combinations according C index. LncRNA Signature (ERLS) model constructed multivariate regression. median risk score datasets, high- low-risk groups. Kaplan-Meier survival analysis, time-dependent ROC, immune cell infiltration, immunotherapy response, checkpoints analyzed. Results 64 subjected a machine-learning process. stepCox (forward) combined Ridge algorithm, 20 lncRNA ERLS model. showed that high-risk group had lower rate. area under curve (AUC) in predicting OS at 1, 3, 5 years 0.758, 0.816, 0.827 entire cohort. xCell ssGSEA higher may contribute activation cytolytic activity, inflammation promotion, T-cell co-stimulation pathways. expression levels PDL1, CTLA4, TMB. can predict response anti-PD1 anti-CTLA4 therapy. Patients low PDL1 or high CTLA4 exhibited significantly better prospects, whereas poorest outcomes. Conclusion Our study an prognostic optimizing clinical management patients.

Language: Английский

---

Cuproptosis Regulation by Long Noncoding RNAs: Mechanistic Insights and Clinical Implications in Cancer

Archives of Biochemistry and Biophysics, Journal Year: 2025, Volume and Issue: unknown, P. 110324 - 110324

Published: Feb. 1, 2025

Language: Английский

---

Big data analysis and machine learning of the role of cuproptosis-related long non-coding RNAs (CuLncs) in the prognosis and immune landscape of ovarian cancer

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 25, 2025

Ovarian cancer (OC) is a severe malignant tumor with significant threat to women's health, characterized by high mortality rate and poor prognosis despite conventional treatments such as cytoreductive surgery platinum-based chemotherapy. Cuproptosis, novel form of cell death triggered copper ion accumulation, has shown potential in therapy, particularly through the involvement CuLncs. This study aims identify risk signatures associated CuLncs OC, construct prognostic model, explore therapeutic drugs impact on OC behavior. We analyzed ovarian data (TCGA-OV) from TCGA database, including transcriptomic clinical 376 patients. Using Pearson correlation LASSO regression, we identified 8 signature model. Patients were categorized into high- low-risk groups based their scores. performed survival analysis, model validation, drug sensitivity vitro experiments assess model's performance functional key proliferation, invasion, migration. The demonstrated predictive power, an area under curve (AUC) 0.702 for 1-year, 0.640 3-year, 0.618 5-year survival, outperforming pathological features stage grade. High-risk patients exhibited higher Tumor Immune Dysfunction Exclusion (TIDE) scores, indicating stronger immune evasion ability. Drugs JQ12, PD-0325901, sorafenib showed reduced IC50 values high-risk group, suggesting benefits. In revealed that knockdown LINC01956, CuLnc signature, significantly inhibited migration cells (P<0.05). Our explored targets OC. findings highlight importance response, providing new insights future research applications.

Language: Английский

---

Cuproptosis inhibits tumor progression and enhances cisplatin toxicity in ovarian cancer

The FASEB Journal, Journal Year: 2025, Volume and Issue: 39(6)

Published: March 22, 2025

Abstract Cuproptosis is a novel form of regulated cell death triggered by copper ion and ionophore. While cuproptosis has been actively explored as potential target for cancer therapy, its role in ovarian (OC) still remains unclear. In this study, we demonstrate that inhibits OC proliferation, migration, invasion through FDX1 regulation suppresses tumor growth mouse model. We also confirm enhances sensitivity to cisplatin treatment both vivo vitro. Moreover, our findings reveal affects cholesterol biosynthesis cells, with playing crucial cytotoxic effect. Taken together, results elucidate the effect suggest it promising therapeutic strategy.

Language: Английский

---

Construction of a prognostic model for ovarian cancer based on a comprehensive bioinformatics analysis of cuproptosis-associated long non-coding RNA signatures

Heliyon, Journal Year: 2024, Volume and Issue: 10(15), P. e35004 - e35004

Published: July 23, 2024

Ovarian cancer (OCa) is a common malignancy in women, and the role of cuproptosis its related genes OCa unclear. Using GSE14407 dataset, we analyzed expression correlation cuproptosis-related (CRGs) between tumor normal groups. From TCGA-OV identified 20 long non-coding RNAs (CuLncs) associated with patient survival through univariate Cox analysis. patients were divided into early-stage late-stage groups to analyze CuLncs expression. Cluster analysis classified two clusters, Cluster1 having poorer prognosis. Significant differences "Lymphatic Invasion" "Cancer status" observed clusters. Seven CRGs showed significant differences, validated using human protein atlas (HPA) databases. Immune revealed higher ImmuneScore Cluster1. GSEA signaling pathways. LASSO regression included 11 construct validate prediction model, classifying high-risk low-risk Correlations riskScore, phenotype, ImmuneScore, immune cell infiltration explored. Cell experiments that knocking down AC023644.1 decreases viability. In conclusion, constructed an accurate prognostic model for based on CuLncs, providing basis prognosis assessment potential immunotherapy targets.

Language: Английский

---

Copper homeostasis and cuproptosis in gynecological cancers

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: Sept. 25, 2024

Copper (Cu) is an essential trace element involved in a variety of biological processes, such as antioxidant defense, mitochondrial respiration, and bio-compound synthesis. In recent years, novel theory called cuproptosis has emerged to explain how Cu induces programmed cell death. targets lipoylated enzymes the tricarboxylic acid cycle subsequently triggers oligomerization dihydrolipoamide S-acetyltransferase, leading loss Fe–S clusters induction heat shock protein 70. Gynecological malignancies including cervical cancer, ovarian cancer uterine corpus endometrial carcinoma significantly impact women’s quality life even pose threat their lives. Excessive can promote progression by enhancing tumor growth, proliferation, angiogenesis metastasis through multiple signaling pathways. However, there are few studies investigating gynecological cancers relation cuproptosis. Therefore, this review discusses homeostasis while exploring potential use for prognosis prediction well its implications treatment cancers. Additionally, we explore application ionophore therapy treating malignancies.

Language: Английский

---

Targeting cuproptosis for cancer therapy: Focus on the anti-tumor immune system

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

---

Roles of DEPDC1 in various types of cancer (Review)

Oncology Letters, Journal Year: 2024, Volume and Issue: 28(5)

Published: Aug. 29, 2024

Dishevelled, EGL-10 and pleckstrin domain-containing 1 (DEPDC1) has been identified as a crucial factor in the development progression of various types cancer. This protein, which is largely undetectable normal tissues but highly expressed numerous tumor types, serves significant role cell mitosis, proliferation, migration, invasion, angiogenesis, autophagy apoptosis. Furthermore, DEPDC1 implicated several key signaling pathways, such NF-κB, PI3K/Akt, Wnt/β-catenin Hippo are essential for proliferation survival. The expression linked to poor prognosis survival rates multiple cancer, including hepatocellular carcinoma, lung adenocarcinoma, colorectal cancer breast Notably, suggested have potential diagnostic prognostic marker, well therapeutic target. Its involvement critical pathways suggests that targeting could inhibit growth metastasis, thereby improving patient outcomes. In addition, clinical trials shown promising results DEPDC1-derived peptide vaccines, indicating their safety efficacy treatment. To best our knowledge, this first comprehensive review addressing Through analysis existing studies, present aimed consolidate knowledge highlight gaps understanding, paving way future research elucidate complex interactions context biology.

Language: Английский

---

In Vitro and Vivo Experiments Revealing Astragalin Inhibited Lung Adenocarcinoma Development via LINC00582/miR‐140‐3P/PDPK1

Journal of Biochemical and Molecular Toxicology, Journal Year: 2024, Volume and Issue: 38(12)

Published: Nov. 18, 2024

ABSTRACT This study aimed to explore the mechanism of development lung adenocarcinoma (LUAD) treated by astragalin. Transcriptome sequencing was performed obtain gene profile LUAD Combining with bioinformatics analysis including differential screening, function enrichment (gene ontology and KEGG), ceRNA construction, we obtained novel lncRNA mediated miRNA/mRNA axis. Then, cell experiments were examine role in proliferation, migration invasion, apoptosis for Moreover, tumor formation nude mice carried out detect astragalin vivo. The network obtained, that is, LINC00852 LINC00582/miR‐140‐3p/PDPK1 played an important Function indicated si‐LINC00852 inhibited promoted via miR‐140‐3p/PDPK1 ( p < 0.05, 0.01). animal further confirmed growth through Conversely, this provides comprehensive insights into diagnostic therapeutic implications LINC00582 LUAD, axis drug target treating LUAD.

Language: Английский

---