CENPA promotes glutamine metabolism and tumor progression by up-regulating SLC38A1 in endometrial cancer

Cellular Signalling, Journal Year: 2024, Volume and Issue: 117, P. 111110 - 111110

Published: Feb. 20, 2024

Language: Английский

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PHGDH: a novel therapeutic target in cancer

Experimental & Molecular Medicine, Journal Year: 2024, Volume and Issue: 56(7), P. 1513 - 1522

Published: July 1, 2024

Abstract Serine is a key contributor to the generation of one-carbon units for DNA synthesis during cellular proliferation. In addition, it plays crucial role in production antioxidants that prevent abnormal proliferation and stress cancer cells. recent studies, relationship between metabolism serine biosynthesis pathway has been highlighted. this context, 3-phosphoglycerate dehydrogenase (PHGDH) notable as enzyme functions primary rate-limiting pathway, facilitating conversion 3-phosphohydroxypyruvate. Elevated PHGDH activity diverse cells mediated through genetic amplification, posttranslational modification, increased transcription, allosteric regulation. Ultimately, these characteristics allow not only influence growth progression but also play an important metastasis drug resistance. Consequently, emerged focal point research. review, structural aspects its involvement are investigated, proposed potential therapeutic target cancers. By elucidating how expression promotes growth, goal review provide insight into innovative treatment strategies. This paper aims reveal inhibitors can overcome resistance mechanisms, contributing development effective treatments.

Language: Английский

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Glutamine and amino acid metabolism as a prognostic signature and therapeutic target in endometrial cancer

Cancer Medicine, Journal Year: 2023, Volume and Issue: 12(15), P. 16337 - 16358

Published: June 30, 2023

Abstract Introduction Endometrial cancer (EC) is the most common female reproductive system in developed countries with growing incidence and associated mortality, which may be due to prevalence of obesity. Metabolism reprogramming including glucose, amino acid, lipid remodeling a hallmark tumors. Glutamine metabolism has been reported participate tumor proliferation development. This study aimed develop glutamine metabolism‐related prognostic model for EC explore potential targets treatment. Method Transcriptomic data survival outcome were retrieved from The Cancer Genome Atlas (TCGA). Differentially expressed genes related recognized utilized build by univariate multivariate Cox regressions. was confirmed training, testing, entire cohort. A nomogram combing clinicopathologic features established tested. Moreover, we explored effect key metabolic enzyme, PHGDH, on biological behavior cell lines xenograft model. Results Five genes, OTC, ASRGL1, ASNS, NR1H4, involved construction. Kaplan–Meier curve suggested that patients as high risk underwent inferior outcomes. receiver operating characteristic (ROC) showed sufficient predict survival. Enrichment analysis DNA replication repair dysfunction high‐risk whereas immune relevance revealed low scores group. Finally, integrating clinical factors created verified. Further, knockdown PHGDH growth inhibition, increasing apoptosis, reduced migration. Promisingly, NCT‐503, inhibitor, significantly repressed vivo ( p = 0.0002). Conclusion Our work validated favorably evaluates prognosis patients. crucial point linked metabolism, acid progression. High‐risk stratified not therapy. might target links serine well

Language: Английский

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Insomnia and Female Reproductive Diseases: A Cross-Sectional and Mendelian Randomization Study

International Journal of Women s Health, Journal Year: 2025, Volume and Issue: Volume 17, P. 439 - 447

Published: Feb. 1, 2025

Insomnia is increasingly emerging as a significant concern in public health, with longstanding emphasis on its relationship overall well-being. Nevertheless, few research has been devoted to investigating the between insomnia and female reproductive health. In our study, we conducted Mendelian randomization (MR) study estimate causal diseases. A total of 268 independent genetic variants associated at genome-wide significance level (P < 5×10-8) were used instrumental variables. Summary-level data obtained from UK Biobank Finn Gen including ovarian cysts, polycystic syndrome (PCOS), endometriosis, premature insufficiency (POI), cancer (OC), uterine fibroids, endometrial (EC) infertility. We performed logistic regression assess associations risk OC EC by using National Health Nutrition Examination Survey (NHANES) 2013-2014. Our reveals that liability constitutes factor for cysts (odds ratio [OR]: 1.44, 95% confidence interval [CI]: 1.21-1.72, P< 0.05), PCOS (OR: 1.67, CI: 1.44-1.94, endometriosis 1.43, 1.16-1.76, 0.05). However, found no statistically POI, OC, EC, or Additionally, body mass index (BMI) was mediate about 10% effect PCOS. Moreover, cross-sectional not EC. provides evidence genetically predicted increases PCOS, endometriosis. Accordingly, potential weight control good sleep keeping fit need be emphasized.

Language: Английский

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Endometrial Cancer Is Associated with Altered Metabolism and Composition of Fatty Acids

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 3322 - 3322

Published: April 2, 2025

Endometrial cancer (EC) is a complex gynecologic malignancy that requires deeper understanding of its molecular basis to improve therapeutic strategies. In this study, we investigated the role fatty acid (FA) reprogramming in progression EC. We analyzed FA profiles identify stage-specific changes and gene expression key enzymes involved synthesis, desaturation, elongation, transport, oxidation at different stages Our results show EC tissues have lower levels saturated branched-chain FA, higher very long-chain n-3 polyunsaturated (PUFA), monounsaturated with exception myristoleic acid. The differences n-6 PUFA were inconsistent. Gene analysis revealed upregulation controlling de novo including ACACA, FASN, SCD1, ELOVL1. contrast, genes related transport cell β-oxidation was downregulated. some metabolism upregulated, while others These demonstrate lipid suggest potential targets for novel interventions

Language: Английский

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Transcriptional regulation by PHGDH drives amyloid pathology in Alzheimer’s disease

Cell, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

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Urine and serum metabolomic analysis of endometrial cancer diagnosis and classification based on ultra-performance liquid chromatography mass spectrometry

Metabolomics, Journal Year: 2024, Volume and Issue: 20(1)

Published: Jan. 28, 2024

Language: Английский

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Dual targeting of glutamine and serine metabolism in acute myeloid leukemia

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

Published: April 16, 2024

Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy characterized by disrupted blood cell production and function. Recent investigations have highlighted the potential of targeting glutamine metabolism as promising therapeutic approach for AML. Asparaginases, enzymes that deplete circulating asparagine, are approved treatment acute lymphoblastic leukemia, but also under investigation in AML, with results. We previously reported an elevation plasma serine levels following Erwinia -derived asparaginase (also called crisantaspase). This led us to hypothesize AML cells initiate de novo biosynthesis pathway response crisantaspase inhibiting this combination would enhance death. Here we report lines, clinically available crisantaspase, Rylaze, upregulates phosphoglycerate dehydrogenase (PHGDH) phosphoserine aminotransferase (PSAT1) through activation Amino Acid Response (AAR) pathway, cellular stress mechanism regulates amino acid protein synthesis conditions nutrient limitation. Inhibition CRISPR- Cas9 -mediated knockout PHGDH resulted ~250-fold reduction half-maximal inhibitory concentration (IC 50 ) indicating heightened sensitivity therapy. Treatment Rylaze small molecule inhibitor (BI4916) revealed synergistic anti-proliferative effects both lines primary patient samples. Rylaze-BI4916 inhibition cap-dependent mRNA translation synthesis, well marked decrease intracellular glutathione levels, critical antioxidant. Collectively, our results highlight clinical novel strategy

Language: Английский

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A critical review of advances in tumor metabolism abnormalities induced by nitrosamine disinfection by-products in drinking water

Toxicological Sciences, Journal Year: 2024, Volume and Issue: 199(1), P. 12 - 28

Published: Jan. 30, 2024

Abstract Intensified sanitation practices amid the recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak might result in increased release of chloramine disinfectants into surface water, significantly promoting formation nitrosamine disinfection by-products (DBPs) drinking water. Unfortunately, these DBPs exhibit significant genotoxic, carcinogenic, and mutagenic properties, whereas chlorinating remain global practice. The current review provides valuable insights occurrence, identification, contamination status, exposure limits, toxicity new unregulated (nitrosamine DBPs) As a result, concentrations far exceed allowable limits prolonged has potential to cause metabolic disorders, critical step tumor initiation progression. Importantly, based on research, we have concluded role nitrosamines different pathways. Remarkably, can induce chronic inflammation initiate tumors by activating sphingolipid polyunsaturated fatty acid metabolism. Regarding amino nucleotide metabolism, inhibit tryptophan metabolism de novo synthesis. Moreover, inhibition synthesis fails repair DNA damage induced nitrosamines. Additionally, accumulation lactate may act as pivotal signaling molecule communication within microenvironment. However, with advancement metabolomics, understanding causing cancer inducing abnormalities lags behind, specific mechanisms toxic effects are not clearly defined. Urgently, further studies exploring this promising area needed.

Language: Английский

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MKRN1 regulates the expression profiles and transcription factor activity in HeLa cells inhibition suppresses cervical cancer cell progression

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: March 13, 2024

Abstract Cervical cancer is one of the most common gynecologic malignancies worldwide, necessitating identification novel biomarkers and therapeutic targets. This study aimed to investigate significance MKRN1 in cervical explore its potential as a diagnostic marker target. The results indicated that expression was up-regulated tissues correlated with advanced tumor stage, higher grade, poor patient survival. Functional studies demonstrated targeting effectively inhibited cell proliferation, migration, invasion, highlighting critical role progression metastasis. Moreover, knockdown resulted altered patterns six transcription factor-encoding genes, revealing involvement gene regulation. Co-expression network analysis unveiled complex regulatory mechanisms underlying effects on expression. Furthermore, suggested might serve for personalized treatment strategies target inhibit growth, metastasis, overcome drug resistance. development MKRN1-targeted interventions hold promise advancing medicine approaches treatment. Further research warranted validate these findings, elucidate mechanisms, translate insights into improved management outcomes patients.

Language: Английский

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