Tumor associated macrophages transfer ceruloplasmin mRNA to fibrosarcoma cells and protect them from ferroptosis

Redox Biology, Год журнала: 2024, Номер 71, С. 103093 - 103093

Опубликована: Фев. 17, 2024

Solid tumors are characterized by hypoxic areas, which prone for macrophage infiltration. Once infiltrated, macrophages polarize to tumor associated (TAM) support progression. Therefore, the crosstalk between TAMs and cells is of current interest development novel therapeutic strategies. These may comprise induction an iron- lipid peroxidation-dependent form cell death, known as ferroptosis. To study - we polarized primary human towards a TAM-like phenotype, co-cultured them with HT1080 fibrosarcoma cells, analyzed response ferroptosis induction. In expression ceruloplasmin mRNA increased, was driven hypoxia inducible factor 2 signal transducer activator transcription 1. Subsequently, transferred from via extracellular vesicles. translated into protein protect RSL3-induced Mechanistically this based on reduced iron abundance peroxidation. Interestingly, in naïve also induced under co-culture recapitulated protective effect observed TAM co-cultures. conclusion, provoke release thereby peroxidation/ferroptosis.

Язык: Английский

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Novel LncRNA LINC02936 Suppresses Ferroptosis and Promotes Tumor Progression by Interacting with SIX1/CP Axis in Endometrial Cancer

International Journal of Biological Sciences, Год журнала: 2024, Номер 20(4), С. 1356 - 1374

Опубликована: Янв. 1, 2024

Endometrial cancer (EC) is a prevalent gynecological malignancy, and metabolic disorders are among its most significant risk factors.Abnormal iron metabolism associated with the progression of malignancy.Nevertheless, involvement in EC remains uncertain.Ceruloplasmin (CP) functions as multicopper oxidase ferroxidase, playing crucial role maintaining balance between copper iron.Prior research has demonstrated that dysregulated expression CP important clinical implications EC.However, specific underlying molecular mechanisms uncertain.This examined impact on malignant advancement by suppressing ferroptosis.Next, we explored possibility Long non-coding RNA (lncRNA) LINC02936/SIX1/CP axis may be key pathway for inhibiting ferroptosis promoting EC.Mechanistically, SIX1 modulates CP, whereas LINC02936 interacts recruits to promoter, leading upregulation inhibition ferroptosis, promotion progression.Administration small peptide cloud block LINC02936-SIX1 interaction, thereby inhibits ferroptosis.Altogether, this first report lncRNA regulation EC.Our enhances knowledge lncRNA-mediated indicates potential therapeutic significance treating EC.

Язык: Английский

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Chemical background of silver nanoparticles interfering with mammalian copper metabolism

Journal of Hazardous Materials, Год журнала: 2023, Номер 451, С. 131093 - 131093

Опубликована: Фев. 26, 2023

Язык: Английский

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Integration of Single-Cell RNA Sequencing and Bulk RNA Sequencing Data to Establish and Validate a Prognostic Model for Patients With Lung Adenocarcinoma

Frontiers in Genetics, Год журнала: 2022, Номер 13

Опубликована: Янв. 27, 2022

Background: Lung adenocarcinoma (LUAD) remains a lethal disease worldwide, with numerous studies exploring its potential prognostic markers using traditional RNA sequencing (RNA-seq) data. However, it cannot detect the exact cellular and molecular changes in tumor cells. This study aimed to construct model for LUAD single-cell RNA-seq (scRNA-seq) Methods: Bulk data were downloaded from The Cancer Genome Atlas (TCGA) database. scRNA-seq acquired Gene Expression Omnibus (GEO) uniform manifold approximation projection (UMAP) was used dimensionality reduction cluster identification. Weighted Correlation Network Analysis (WGCNA) utilized identify key modules differentially expressed genes (DEGs). non-negative Matrix Factorization (NMF) algorithm different subtypes based on DEGs. Cox regression analysis develop model. characteristics of mutation landscape, immune status, checkpoint inhibitors (ICIs) related between risk groups also investigated. Results: four samples integrated 13 clusters 9cell types. After applying differential analysis, NK cells, bladder epithelial bronchial cells identified as significant cell Overall, 329 DEGs selected construction through WGCNA. Besides, NMF two TCGA cohort, distinct prognosis being observed. We developed expression levels six A higher score significantly correlated poor survival outcomes but associated more frequent TP53 rate, burden (TMB), up-regulation PD-L1. Two independent external validation cohorts adopted verify our results, consistent results observed them. Conclusion: constructed validated by integrating 10× bulk we this population, characteristics.

Язык: Английский

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Cuproptosis-related modification patterns depict the tumor microenvironment, precision immunotherapy, and prognosis of kidney renal clear cell carcinoma

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Сен. 23, 2022

Background Due to the different infiltration abundance of immune cells in tumor, efficacy immunotherapy varies widely among individuals. Recently, growing evidence suggested that cuproptosis has impact on cancer immunity profoundly. However, comprehensive roles cuproptosis-related genes tumor microenvironment (TME) and response are still unclear. Methods Based 43 genes, we employed unsupervised clustering identify patterns single-sample gene set enrichment analysis algorithm build a signature for individual patient’s cell checkpoint blockade (ICB) evaluation. Then, were narrowed down using univariate Cox regression model least absolute shrinkage selection operator algorithm. Finally, risk score was built by random survival forest based these narrowed-down genes. Results Two distinct developed, with cluster 1 showing better prognosis higher immune-related pathways cells. For evaluation, could be used not only predicting TME but also evaluating an individual’s sensitivity ICBs. Patients scores exhibited more activated processes, infiltration, curative Furthermore, robust indicated patients showed worse outcomes, which validated internal external validation cohorts. Ultimately, nomogram combined prognostic clinical factors it excellent prediction accuracy outcomes. Conclusion Distinct have significant differences kidney renal clear carcinoma (KIRC). Cuproptosis able provide guidance precision therapy accurate KIRC.

Язык: Английский

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Adipose tissue-to-breast cancer crosstalk: Comprehensive insights

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Год журнала: 2022, Номер 1877(5), С. 188800 - 188800

Опубликована: Сен. 1, 2022

Язык: Английский

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Copper-related genes predict prognosis and characteristics of breast cancer

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Апрель 27, 2023

Background The role of copper in cancer treatment is multifaceted, with homeostasis-related genes associated both breast prognosis and chemotherapy resistance. Interestingly, elimination overload have been reported to therapeutic potential treatment. Despite these findings, the exact relationship between homeostasis development remains unclear, further investigation needed clarify this complexity. Methods pan-cancer gene expression immune infiltration analysis were performed using Cancer Genome Atlas Program (TCGA) dataset. R software packages employed analyze mutation status samples. After constructing a model separate samples by LASSO-Cox regression, we examined statement, survival status, drug sensitivity metabolic characteristics high- low-copper related scoring groups. We also studied constructed human protein atlas database analyzed their pathways. Finally, staining was clinical sample investigate distribution tissue paracancerous tissue. Results Pan-cancer showed that copper-related are cancer, profile significantly different from other cancers. essential regression ATP7B (ATPase Copper Transporting Beta) DLAT (Dihydrolipoamide S-Acetyltransferase), whose enriched cell cycle pathway. group presented higher levels activation, better probabilities survival, enrichment pathways pyruvate metabolism apoptosis, drugs. Immunohistochemistry high Conclusion This study displayed impacts on overall infiltration, which could predict patients’ tumor statement. These findings may serve support future research efforts aiming at improving management cancer.

Язык: Английский

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9S1R nullomer peptide induces mitochondrial pathology, metabolic suppression, and enhanced immune cell infiltration, in triple-negative breast cancer mouse model

Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 170, С. 115997 - 115997

Опубликована: Дек. 20, 2023

Nullomers are the shortest strings of absent amino acid (aa) sequences in a species or group species. Primes those nullomers that have not been detected genome any 9S1R is 5-aa peptide prime sequence attached to 5-arginine aa, used treat triple negative breast cancer (TNBC) an vivo mouse model. This unique peptide, administered with trehalose carrier (9S1R-NulloPT), offers enhanced solubility and exhibits distinct anti-cancer effects against TNBC. In our study, we investigated effect 9S1R-NulloPT on tumor growth, metabolism, metastatic burden, immune-microenvironment (TME), transcriptome aggressive TNBC tumors. Notably, treated mice had smaller tumors initial phase treatment, as compared untreated control, diminished ex bioluminescence at later-stages - indicative metabolically quiescent, dying The treatment also caused changes TME increased infiltration immune cells altered transcriptome, 365 upregulated genes 710 downregulated genes. Consistent vitro data, were enriched cellular metabolic processes (179), specifically mitochondrial TCA cycle/oxidative phosphorylation (44), translation machinery/ribosome biogenesis (45). associated developmental (13), ECM organization (12) focal adhesion pathways (7). conclusion, study demonstrates effectively reduced growth during its phase, altering transcriptome. induced pathology which led deceleration tumors, aligning observations.

Язык: Английский

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Determination of copper and other trace elements in serum samples from patients with biliary tract cancers: prospective noninterventional nonrandomized clinical study protocol

Radiology and Oncology, Год журнала: 2024, Номер 58(2), С. 300 - 310

Опубликована: Март 29, 2024

Abstract Background Biliary tract cancers (BTCs) are usually diagnosed at an advanced stage, when the disease is incurable. Currently used tumor biomarkers have limited diagnostic value for BTCs, so there urgent need sensitive and specific their earlier diagnosis. Deregulation of homeostasis trace elements involved in carcinogenesis different cancers, including BTCs. The objective study to determine/compare total concentrations copper (Cu), zinc (Zn) iron (Fe) proportions free Cu bound ceruloplasmin (Cp) isotopic ratio 65 Cu/ 63 serum samples from healthy volunteers cancer patients using inductively coupled plasma-mass spectrometry-based methods (ICP-MS). Patients In this prospective, noninterventional, nonrandomized 20 will be enrolled identify Cu, Zn Fe levels, fractionation as a predictive biomarker response systemic therapy which evaluated by computed tomography. Newly developed analytical based on ICP-MS applied metal-based research oncology. Conclusions comparison concentration selected elements, proportion Cp conducted provide foundation development BTC screening methodology data usability potential BTCs therapy.

Язык: Английский

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Identification of RNF213 as a Potential Suppressor of Local Invasion in Intrahepatic Cholangiocarcinoma

Laboratory Investigation, Год журнала: 2024, Номер 104(7), С. 102074 - 102074

Опубликована: Май 7, 2024

Язык: Английский

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