Integrative Analyses of Pyrimidine Salvage Pathway-Related Genes Revealing the Associations Between UPP1 and Tumor Microenvironment

Journal of Inflammation Research, Journal Year: 2024, Volume and Issue: Volume 17, P. 101 - 119

Published: Jan. 1, 2024

Background: The pyrimidine salvage pathway plays a critical role in tumor progression and patient outcomes. roles of pathway-related genes (PSPGs) cancer, however, are not fully understood. This study aims to depict the characteristics PSPGs across various cancers. Methods: An integrative pan-cancer analysis six (CDA, UCK1, UCK2, UCKL1, UPP1, UPP2) was conducted using TCGA data, single-cell RNA sequencing datasets, samples. Single-cell transcriptome RT-qPCR were used validate relation between UPP1 cytokines. Flow cytometry performed immune checkpoint regulation. correlation associated neutrophils (TAN) investigated validated by tissue microarrays (TMAs). Results: showed low mutation rates but significant copy number variations, particularly amplifications UCK2 DNA methylation patterns varied, with notable negative correlations gene expression UPP1. broadly up-regulated multiple cancers, clinical staging prognosis. Proteomic data further confirmed these findings. Functional revealed PSPGs' associations proliferation, metastasis, signaling pathways. strong microenvironment (TME), cytokines, checkpoints, cells. associations, highlighting UPP1's influence on cytokine In esophageal squamous cell carcinoma (ESCC), UPP1-high cells significantly immunosuppressive TME. Spatial TMAs that UPP1+ predominantly located at invasive margin closely neutrophils, correlating poorer Conclusion: Our depicted multi-dimensional view particular focus Targeting holds promise as potential strategy for cancer therapy. Keywords: pathways,

Language: Английский

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Non-canonical role of UCKL1 on ferroptosis defence in colorectal cancer

EBioMedicine, Journal Year: 2023, Volume and Issue: 93, P. 104650 - 104650

Published: June 19, 2023

Pyrimidine nucleotides fuel the growth of colorectal cancer (CRC), making their associated proteins potential targets for intervention. Uridine-Cytidine Kinase Like-1(UCKL1) is an enzyme involved in pyrimidine salvage pathway. It highly expressed multiple cancers. But function and underlying mechanism UCKL1 CRC are yet to study.Large-scale genomic analysis was performed search players related metabolism. The were examined by RNA interference coupled with vitro vivo assays. GSH/GSSG assay, NADP+ ROS, Lipid peroxidation assays check ferroptosis. Metabolomics analyses, sequencing, western blotting, rescue done reveal mechanisms UCKL1. Xenograft mouse model used examine therapeutic as a target combination other ferroptosis inducers.UCKL1 identified repress cells. CRC. regulated cells proliferation migration. Downregulation led enhanced tumour lipid peroxidation. Intriguingly, reduction-mediated not its role catalyzing uridine monophosphate (UMP) cytidine (CMP) synthesis. Instead, stabilized Nrf2, which turn promoted expression SLC7A11, classical repressor Moreover, downregulation sensitized GPX4 inhibitors vivo.Our study demonstrates that plays non-canonical repressing through UCKL1-Nrf2-SLC7A11 axis Combinatorial strategy targeting depletion application may serve new effective method treatment.This supported part fund from National Natural Science Foundation China (Grant No. 31970674 PY), Basic Applied Research Program Guangdong Province 2023A1515030245 KL), program Provincial Clinical Center Digestive Diseases (2020B1111170004), Key Discipline.

Language: Английский

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Analyzing aberrant DNA methylation in colorectal cancer uncovered intangible heterogeneity of gene effects in the survival time of patients

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: Dec. 13, 2023

Abstract Colorectal cancer (CRC) involves epigenetic alterations. Irregular gene-methylation alteration causes and advances CRC tumor growth. Detecting differentially methylated genes (DMGs) in patient survival time paves the way to early detection prognosis. However, data including times are heterogeneous. Almost all studies tend ignore heterogeneity of DMG effects on survival. To this end, we utilized a sparse estimation method finite mixture accelerated failure (AFT) regression models capture such heterogeneity. We analyzed dataset normal colon tissues identified 3406 DMGs. Analysis overlapped DMGs with several Gene Expression Omnibus datasets led 917 hypo- 654 hyper-methylated pathways were revealed via gene ontology enrichment. Hub selected based Protein–Protein-Interaction network SEMA7A , GATA4 LHX2 SOST CTLA4 regulating Wnt signaling pathway. The relationship between DMGs/hub uncovered two-component AFT model. NMNAT2 ZFP42 NPAS2 MYLK3 NUDT13 KIRREL3 FKBP6 hub NFATC1 TLE4 associated most aggressive form disease that can serve as potential diagnostic targets for detection.

Language: Английский

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Exploration of phosphoproteomic association during epimorphic regeneration

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 10, 2025

Unravelling the intricate patterns of site-specific protein phosphorylation during Epimorphic regeneration holds key to unlocking secrets tissue complexity. Understanding these precise modifications and their impact on function could shed light remarkable regenerative capacity tissues, with potential implications for therapeutic interventions. In this study we have systematically mapped global within regenerating zebrafish caudal fins, elucidating landscape signalling pathway associate process. Based mass spectrometry analysis, identified 440 phosphorylated proteins using immunoprecipitation method phosphoserine, phosphothreonine, phosphotyrosine antibodies, 74 TiO₂ column enrichment were found differentially process from 12 hpa 7 dpa compared control. Interestingly 95% TiO2 also be through phosphoprotein antibody pull down impacting high accuracy significance methods greater association 70 undergoing differential regeneration. Whole mount immunohistochemistry analysis reveals at 1dpa, 2dpa 3dpa time points. Network revealed that cancer-related diseases, organismal injuries abnormalities as most strongly associated canonical network pathways expressed phosphoproteome in mechanism This research enhances our comprehension post-translational modification context fin regeneration, shedding its prospective application field medicine.

Language: Английский

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Unveiling the role of tyrosine kinases in doxorubicin-induced cardiotoxicity and beyond

Cardiovascular Research, Journal Year: 2025, Volume and Issue: unknown

Published: March 13, 2025

Language: Английский

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Integrated transcriptomics and metabolomics analyses to investigate the anticancer mechanisms of cinobufagin against liver cancer through interfering with lipid, amino acid, carbohydrate, and nucleotide metabolism

Bioorganic Chemistry, Journal Year: 2022, Volume and Issue: 130, P. 106229 - 106229

Published: Oct. 30, 2022

Language: Английский

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The Impact of Pigment-Epithelium-Derived Factor on MCF-7 Cell Metabolism in the Context of Glycaemic Condition

Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(8), P. 2140 - 2140

Published: Aug. 14, 2023

Studies have demonstrated that pigment-epithelium-derived factor (PEDF) is a robust inhibitor of tumour growth and development, implying this may serve as promising target for therapeutic intervention. However, the precise impact PEDF on cancerous cell metabolic pathways remains uncertain despite ongoing research. In light, study aimed to employ metabolomics approach understanding reprogramming events in breast cancer across different glycaemic loads their response PEDF. Gas chromatography-quadrupole mass spectrometry (GC/Q-MS) analysis revealed alterations ER+ human line MCF-7 cells treated with under varying conditions. The identification significantly altered metabolites was accomplished through MetaboAnalyst (v.5.0) R packages, which enabled both multivariate univariate analyses. Out 48 identified, 14 were chosen based significant conditions treatment (p < 0.05, VIP > 0.8). Dysregulation associated amino acid metabolism, intermediates TCA cycle, nucleotide lipid metabolism detected, they exhibited responses Our results suggest has diverse influence normo- hyperglycaemic environments, thereby warranting studies using patient samples correlate our findings clinical future.

Language: Английский

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Immune-phenotyping and transcriptomic profiling of blood monocytes from patients with breast cancer under neoadjuvant chemotherapy

Advances in molecular oncology, Journal Year: 2024, Volume and Issue: 11(1), P. 79 - 89

Published: April 5, 2024

Introduction. Chemotherapy is a common treatment for breast cancer. Chemotherapeutic drugs effect blood monocytes, which are major contributors to cancer pathogenesis. However, date, pro-tumor or anti-tumor programming by chemotherapy of monocytes controversial. Aim. To characterize changes in phenotypic and transcriptomic profiles patients before after chemotherapeutic treatment. Materials methods . In cohort 50 patients, monocyte populations were identified based on their expression CD14, CD16, CD163, HLA-DR evaluated flow cytometry neoadjuvant chemotherapy. Bulk RNA sequencing was adopted explore the profile CD14 + After treatment, we observed an increase activity signaling pathways related lipid metabolism intracellular transport vesicles from endoplasmic reticulum, against background decreased response exposure interferon γ α, foreign molecules (exogenous nucleic acids, viruses bacteria). Results. 16 monocytes. Under cytostatic increased gene MGLL , NR4A2 UCK1 YOD1 ABCA2 PAPSS2 ATP10 (log2FoldChange ≥0.8; false discovery rate (FDR) ≤0.01) KPNA2 ERCC4 JAGN1 RUBCNL SMYD4 B3GALT4 FDR patients. Using discriminant analysis, relative numbers – - found be valuable predicting Conclusion. Thus, association with revealed.

Language: Английский

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Enzymatic phosphorylation of uridine and cytidine using calcium‐based dual‐enzyme nanoflowers

Food Bioengineering, Journal Year: 2024, Volume and Issue: 3(2), P. 151 - 159

Published: June 1, 2024

Abstract Nucleotides, such as uridine 5′‐monophosphate (5′‐UMP) and cytidine (5′‐CMP), are heavily demanded food additives, dietary supplements, medicinal intermediates. Although enzymatic phosphorylation is an effective approach to producing these nucleosides, its practical application challenging due the need for expensive enzymes coenzyme guanosine‐5′‐triphosphate (GTP). Here we prepared biocompatible calcium‐based nanoflowers incorporated with cascade enzymes, uridine‐cytidine kinase (UCK) acetate (ACK), production of nucleotides. The spatial distribution was optimized maximize their catalytic performances. most active (Ca 3 (PO 4 ) 2 & ACK)& UCK that display rate‐limiting enzyme on outer layer were used in a packed‐bed reactor continuous synthesis 5′‐UMP 5′‐CMP. performance catalyst retained over 80% within 10 h, showing good operational stability.

Language: Английский

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Sex modulates the human genome regulatory network during heart failure and aging.

Research Square (Research Square), Journal Year: 2022, Volume and Issue: unknown

Published: Nov. 11, 2022

Abstract Heart failure and other cardiomyopathies have distinct presentations in males versus females that are often overlooked, leading to ineffective treatment the growing mortality from heart diseases. Understanding sex dimorphism pathogenesis of disease can guide improved diagnostics sex-specific therapy. Thus, we aimed investigate promoter enhancer activity aging. We applied cap analysis gene expression (CAGE) characterize transcribed regulatory elements (TRE) 17 male 14 female healthy failing hearts. show TREs exhibit significant spread throughout entire genome atria ventricles related immune system, metabolic, cardiomyocyte function, developmental pathways. Moreover, found 720 genes with sex-dependent switching, which 40 switched dominant promoters. One example was CREM , a transcription factor short repressive isoform exclusive for males. is extensive β-adrenergic receptor stimulation leads failure, hypertrophy, arrhythmia. Furthermore, identified aging hearts associated metabolic pathways, respectively. also showed patterns, such as age-specific usage 1,100 behaved differently depending on sex, including UCKL1 HAND2 linked uridine metabolism cardiac development, In conclusion, report evidence exhibited hundreds health, pathogenesis,

Language: Английский

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