Carboplatin-resistance-related DNA damage repair prognostic gene signature and its association with immune infiltration in breast cancer

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

Published: Jan. 29, 2025

Introduction Breast cancer is among the most prevalent malignant tumors globally, with carboplatin serving as a standard treatment option. However, resistance often compromises its efficacy. DNA damage repair (DDR) pathways are crucial in determining responses to and also associated immune infiltration. This study aimed identify DDR genes involved elucidate their effects on prognosis, infiltration, drug sensitivity breast patients. Methods A 3D-culture model resistant was constructed sequenced. Co-expressed were analyzed develop predictive model. Immune infiltration analysis tools employed assess microenvironment of patients varying expression levels these risk genes. Additionally, predictions made evaluate efficacy other damage-related drugs across different groups. Molecular assays performed investigate role key gene TONSL cancer. Results By integrating data from public database, we established prognostic signature comprising thirteen Our indicated that this patterns patients, particularly concerning CD8+ T cells NK cells. it demonstrated significant correlation DDR-related drugs, suggesting potential biomarker for Compared control group, TONSL-knockdown cell lines exhibited diminished response DNA-damaging agents, marked by notable increase enhanced sensitivity. Furthermore, single-cell revealed elevated dendritic epithelial cells, triple-negative cancers. Conclusions Carboplatin resistance-related may serve therapeutic target cancer, indicating new strategies

Language: Английский

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Exposing the cellular situation: findings from single cell RNA sequencing in breast cancer

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

Published: March 6, 2025

Breast Cancer (BC) ranks among the top three most prevalent cancers globally and stands as principal contributor to cancer-related fatalities women. In spite of substantial occurrence rate BC, early stage this disease is generally regarded curable. However, intra-tumor heterogeneity presents a formidable obstacle success effective treatment. research, single cell RNA sequencing was utilized dissect tumor microenvironment within BC. Slingshot, CytoTRACE Monocle 2 were applied illustrate differentiation process each subpopulation in pseudotime sequence. To comprehensively comprehend cells (TCs) an analysis upstream transcription factors carried out via pySCENIC, while downstream pathway enrichment conducted through KEGG, GO GSEA. The prognosis model established based on bulk data obtained from TCGA GEO databases. Knock-down experiments also implemented explore function factor CEBPD TCs. Our in-depth identified eight types. Notably, TCs predominantly found epithelial cells. classification further uncovered five unique subpopulations, with one characterized by high UGDH expression. This shown possess distinct metabolic features metabolism-related investigations. intricate communication modalities different types effectively demonstrated means CellChat. Additionally, crucial factor, CEBPD, identified, which pronounced propensity towards tumors harbored potential tumor-advancing characteristics. Its role promoting cancer subsequently verified vitro knock-down experiments. Moreover, prognostic developed, risk score genes incorporated model. Through comparing prognoses UTRS levels, it determined that group had less favorable prognosis. These outcomes contributed elucidation complex interrelationships BC microenvironment. By specifically targeting certain subpopulations TCs, novel treatment strategies could potentially be devised. study shed light direction future research should take, furnishing valuable information can enhance regimens.

Language: Английский

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Endogenous protein S100A14 stabilizes glutaminase to render hepatocellular carcinoma resistant to sorafenib

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: April 11, 2025

Many cases of advanced hepatocellular carcinoma (HCC) are resistant to the widely used drug sorafenib, which worsens prognosis. While many studies have explored how acquired resistance emerges during exposure, mechanism underlying primary before treatment still remain elusive. Single-cell lineage tracing and RNA sequencing were performed identify sorafenib-resistant lineages in HCC. Differential gene expression analysis was employed biomarkers drug-resistant cells. Cell viability colony formation assays adopted assess involvement S100A14 on sorafenib resistance. Co-immunoprecipitation (CO-IP) mass spectrometry conducted uncover downstream targets regulatory mechanisms sorafenib. In vivo mouse xenograft experiments carried out effect or its interacting protein glutaminase (GLS) identified a cluster cells, S100A14, Ca2+-binding protein, determined be critical biomarker for Knockdown significantly increases sensitivity HCC Mechanistically, binds GLS blocks phosphorylation at residues Y308 S314, turn inhibits ubiquitination subsequent degradation. By stabilizing GLS, reduces oxidative stress thereby antagonizing sorafenib-induced apoptosis. Inhibiting improved efficacy against tumors vivo. Our results demonstrate that plays pivotal role promoting by reduce stress, acts as potential therapeutic target enhance patients.

Language: Английский

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Ferroptosis and its role in gastric and colorectal cancers

Korean Journal of Physiology and Pharmacology, Journal Year: 2024, Volume and Issue: 28(3), P. 183 - 196

Published: April 29, 2024

Ferroptosis is a novel mechanism of programmed cell death, characterized by intracellular iron overload, intensified lipid peroxidation, and abnormal accumulation reactive oxygen species, which ultimately resulting in membrane impairment demise.Research has revealed that cancer cells exhibit greater demand for compared to normal cells, indicating potential susceptibility ferroptosis.Stomach colorectal cancers are common gastrointestinal malignancies, their elevated occurrence mortality rates render them global health concern.Despite significant advancements medical treatments, certain unfavorable consequences drug resistance persist.Consequently, directing attention towards the phenomenon ferroptosis gastric holds promise enhancing therapeutic efficacy.This review aims elucidate intricate cellular metabolism associated with ferroptosis, encompassing amino acid metabolism, as well metabolic processes.Furthermore, significance context thoroughly examined discussed.

Language: Английский

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Translational studies of exosomes in sports medicine – a mini-review

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 8, 2024

This review in sports medicine focuses on the critical role of exosomes managing chronic conditions and enhancing athletic performance. Exosomes, small vesicles produced by various cells, are essential for cellular communication transporting molecules like proteins nucleic acids. Originating from endoplasmic reticulum, they play a vital modulating inflammation tissue repair. Their significance is increasingly recognized, particularly healing injuries, improving articular cartilage lesions, osteoarthritic behavior aiding regeneration. Investigations also highlight their potential boosting performance, especially through myocytes-derived that may enhance adaptability to physical training. Emphasizing multidisciplinary approach, this underlines need thoroughly understand exosome biology, including pathways classifications, fully exploit therapeutic potential. It outlines future directions medicine, focusing personalized treatments, clinical evaluations, embracing technological advancements. research represents frontier using improve athletes’ health performance capabilities.

Language: Английский

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Impacts of Nutlin-3a and exercise on murine double minute 2–enriched glioma treatment

Neural Regeneration Research, Journal Year: 2024, Volume and Issue: 20(4), P. 1135 - 1152

Published: March 1, 2024

JOURNAL/nrgr/04.03/01300535-202504000-00029/figure1/v/2024-07-06T104127Z/r/image-tiff Recent research has demonstrated the impact of physical activity on prognosis glioma patients, with evidence suggesting exercise may reduce mortality risks and aid neural regeneration. The role small ubiquitin-like modifier (SUMO) protein, especially post-exercise, in cancer progression, is gaining attention, as are potential anti-cancer effects SUMOylation. We used machine learning to create SUMO-related gene signature (ESLRS). This shows how might help improve outlook for low-grade other cancers. prognostic immunotherapeutic significance ESLRS markers, specifically highlighting murine double minute 2 (MDM2), a component ESLRS, can be targeted by nutlin-3. underscores intricate relationship between natural compounds such nutlin-3 immune regulation. Using comprehensive CRISPR screening, we validated specific genes progression. also revealed insights into effectiveness Nutlin-3a potent MDM2 inhibitor through molecular docking dynamic simulation. inhibited cell proliferation activated p53 pathway. Its efficacy decreased overexpression, this was reversed or exercise. Experiments using mouse model highlighted effect oxidative stress pathway Notably, both administration improved function mice bearing tumors derived from MDM2-overexpressing cells. These results suggest Nutlin-3a, an inhibitor, therapeutic approach management. Our supports use products therapy sheds light interaction exercise, products, regulation treatment.

Language: Английский

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Exercise-regulated lipolysis: Its role and mechanism in health and diseases

Journal of Advanced Research, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

Language: Английский

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Ferroptosis-associated gene CISD2 suppresses colon cancer development by regulating tumor immune microenvironment

PeerJ, Journal Year: 2023, Volume and Issue: 11, P. e15476 - e15476

Published: June 5, 2023

Despite the association of ferroptosis with various tumors, specific mechanism by which it influences colon adenocarcinoma (COAD) microenvironmental equilibrium remains elusive. This study aims to elucidate how affects COAD homeostasis and its potential impact on research.By employing genetic screening single-cell analysis tumor data, we investigated role genes in homeostasis. The were correlated immune cell infiltration tissue samples patient outcomes.Ferroptosis-associated initially identified through FerrDb database. Utilizing tidyverse Seurat packages, substantial expression differences extracted, clustering was performed data. A Venn diagram depicted shared differential for tumors. To screen key genes, further enrichment conducted. Lastly, human lines employed overexpress CDGSH iron sulfur domain 2 (CISD2) cellular assays validate function COAD.Following Cancer Genome Atlas (TCGA) Genotype-Tissue Expression (GTEx) databases, 414 341 normal included. Through database, 259 identified. Clustering data revealed 911 marker 18 genes. Analysis variance (ANOVA) univariate regression determined that only CISD2 statistically significantly associated clinical outcomes. Additionally, found positively correlate activated memory T cells negatively regulatory (Tregs) plasma COAD, as well being several immune-related cancer-related pathways. elevated most likely due cycle regulation system activation. Moreover, upregulation inhibited proliferation enhanced 5-fluorouracil (5-FU) sensitivity. Our findings indicate, first time, governs stimulates impede progression.By modulating mediating infiltration, may inhibit development influencing microenvironment equilibrium, providing valuable insights into relevance research results field.

Language: Английский

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Impact of Physical Exercise on Melanoma Hallmarks: Current Status of Preclinical and Clinical Research

Journal of Cancer, Journal Year: 2023, Volume and Issue: 15(1), P. 1 - 19

Published: Dec. 5, 2023

In recent years, accumulating evidence from preclinical and clinical studies consistently indicated that physical activity/exercise plays a crucial role in reducing the incidence recurrence of various malignancies, by exerting beneficial modulation cancer hallmarks.Moreover, activity is suggested to attenuate certain adverse effects anticancer therapy, including reduction cardiovascular toxicity symptoms related depression anxiety, among others, while preserving muscular strength.In case melanoma, relationship with has been critically debated.Historically, several cohort meta-analyses reported positive association between melanoma risk.This was primarily attributed outdoor activities may expose skin UV radiation, well-known risk factor for melanocyte transformation.However, more does not support such recognizes both prevention progression.Nevertheless, sun protection recommended during training minimize radiation exposure.This narrative review summarizes data about on hallmarks.Specifically, experimental concerning (i) invasion metastasis, (ii) reprogramming energy metabolism, (iii) angiogenesis, (iv) resistance cell death, (v) evasion immune destruction, (vi) tumor-promoting inflammation.

Language: Английский

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Pan-cancer analysis reveals potential immunological and prognostic roles of COA6 in human cancers and preliminary exploration of COA6 in bladder cancer

Cellular Signalling, Journal Year: 2024, Volume and Issue: 117, P. 111111 - 111111

Published: Feb. 22, 2024

Language: Английский

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