The Role of Non-Coding RNAs in Epigenetic Dysregulation in Glioblastoma Development

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(22), С. 16320 - 16320

Опубликована: Ноя. 14, 2023

Glioblastoma (GBM) is a primary brain tumor arising from glial cells. The highly aggressive, the reason for which it has become deadliest type with poorest prognosis. Like other cancers, compromises molecular alteration on genetic and epigenetic levels. Epigenetics refers to changes in gene expression or cellular phenotype without occurrence of any mutations DNA sequence alterations driver tumor-related genes. These are reversible, making them convenient targets cancer therapy. Therefore, we aim review critical dysregulation processes glioblastoma. We will highlight significant affected pathways their outcomes, such as regulation cell cycle progression, growth, apoptosis, angiogenesis, invasiveness, immune evasion, acquirement drug resistance. Examples induced by modifications, alterations, histone post-translational modifications (PTMs), non-coding RNA (ncRNA) regulation, highlighted. As understanding role regulators underlying mechanisms overall pro-tumorigenic landscape glioblastoma essential, this literature study provide valuable insights establishing prognostic diagnostic value various transcripts, including miRNAs.

Язык: Английский

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Single-cell RNA-seq analyses inform necroptosis-associated myeloid lineages influence the immune landscape of pancreas cancer

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Дек. 12, 2023

Introduction Tumor-infiltrating myeloid cells (TIMs) are key regulators in tumor progression, but the similarity and distinction of their fundamental properties pancreatic ductal adenocarcinoma (PDAC) remain elusive. Method In this study, we conducted scRNA-seq data analysis from 12 primary (PT) tissues, 4 metastatic (Met) 3 adjacent normal pancreas tissues (Para), PBMC samples across 16 PDAC patients, revealed a heterogeneous TIMs environment PDAC. Result Systematic comparisons between non-tumor lineages identified 10 necroptosis-associated genes upregulated tumors compared to 5 paratumor or healthy peripheral blood. A novel RTM (resident tissue macrophages), GLUL-SQSTM1- RTM, was found act as positive regulator immunity. Additionally, HSP90AA1+HSP90AB1+ mast exhibited pro-immune characteristics, JAK3+TLR4+ CD16 monocytes were be anti-immune. The findings validated through clinical outcomes cytokines analyses. Lastly, intercellular network reconstruction supported associations clusters, cancer cells, immune cell populations. Conclusion Our comprehensively characterized major three subsets myeloid-derived associated with necroptosis. These not only provide valuable resource for understanding multi-dimensional characterization microenvironment also offer mechanistic insights that can guide design effective immuno-oncology treatment strategies.

Язык: Английский

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The nicotinamide phosphoribosyltransferase antagonist FK866 inhibits growth of prostate tumour spheroids and increases doxorubicin retention without changes in drug transporter and cancer stem cell protein expression

Clinical and Experimental Pharmacology and Physiology, Год журнала: 2020, Номер 48(3), С. 422 - 434

Опубликована: Дек. 21, 2020

Abstract Nicotinamide phosphoribosyltransferase (NAMPT) is a rate‐limiting enzyme for nicotinamide adenine dinucleotide (NAD) synthesis and involved in cancer cell proliferation through regulation of energy production pathways. Therefore, NAMPT inhibitors are promising drugs therapy by limiting supply tumours. Herein, we demonstrated that the inhibitor FK866 ((E)‐N‐(4‐(1‐Benzoylpiperidin‐4‐yl)butyl)‐3‐(pyridin‐3‐yl)acrylamide) dose‐dependently inhibited growth motility DU‐145 prostate tumour spheroids decreased intracellular ATP concentration. The apoptosis marker cleaved caspase‐3 remained unchanged, but autophagy microtubule‐associated protein 1A/1B‐light chain 3 (LC3) was upregulated. Growth inhibition reversed upon co‐administration NAD to culture medium. calcein as well pheophorbide A efflux from increased doxorubicin toxicity, indicating interference with function drug transporters. multicellular expressed stem associated markers CD133, CD44, Oct4, Nanog, Sox2, transporters ABCB1, ABCG2, ABCC1 which properties cells. ABCB1 zosuquidar, ABCG2 Ko143, MK571 retention. Neither expression markers, nor significantly changed treatment. In conclusion, our data suggest inhibits metabolism,

Язык: Английский

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Development of prognostic indicator based on NAD+ metabolism related genes in glioma

Frontiers in Surgery, Год журнала: 2023, Номер 10

Опубликована: Янв. 26, 2023

Background Studies have shown that Nicotinamide adenine dinucleotide (NAD+) metabolism can promote the occurrence and development of glioma. However, specific effects mechanisms NAD+ in glioma are unclear there were no systematic researches about related genes to predict survival patients with Methods The research was performed based on expression data cases Cancer Genome Atlas (TCGA) Chinese Glioma (CGGA) databases. Firstly, TCGA-glioma classified into different subtypes 49 metabolism-related (NMRGs) by consensus clustering. differentially expressed (NMR-DEGs) gotten intersecting NMRGs (DEGs) between normal samples. Then a risk model built Cox analysis least shrinkage selection operator (LASSO) regression analysis. validity verified curves receiver operating characteristic (ROC) curves. In addition, independent prognostic Then, we also identified immune cells, HLA family checkpoints high low groups. Finally, functions at single-cell level explored. Results Consensus clustering two subtypes, overall (OS) differed. A total 11 screened overlapping 5,995 (NMRGs). Next, four genes, PARP9, BST1, NMNAT2, CD38, obtained absolute (Lasso) analyses construct model. OS high-risk group lower. And area under (AUCs) Receiver >0.7 1, 3, 5 years. showed age, grade G3, G4, IDH status, ATRX BCR Scores reliable factors. three Mast cells activated, NK activated B naive, 24 such as HLA-DPA1 HLA-H, 8 checkpoints, ICOS, LAG3, CD274, found significantly relevant proliferation, cell differentiation, apoptosis. Conclusion might be important molecular biomarkers therapeutic targets for patients.

Язык: Английский

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Extracellular Nampt (eNampt/Visfatin/PBEF) directly and indirectly stimulates ACTH and CCL2 protein secretion from isolated rat corticotropes

Advances in Clinical and Experimental Medicine, Год журнала: 2021, Номер 30(9), С. 967 - 980

Опубликована: Авг. 20, 2021

Background.Nicotinamide phosphoribosyltransferase (Nampt/visfatin/PBEF) acts both as an enzyme in the nicotinamide adenine dinucleotide (NAD) synthesis pathway well extracellular hormone (eNampt).Among its effects, eNampt exerts potent pro-inflammatory effects.We have recently shown that, rats, stimulates corticosterone secretion by acting through pituitary rather than hypothalamus.Objectives.To investigate mechanism of action on adrenocorticotropic (ACTH) and chemokine (C-C motif) ligand 2 (CCL2), which are cytokines secreted neuroendocrine tumors. Materials methods.The research was carried out AtT-20 murine cell line, primary rat culture, isolated corticotropes, vivo.The effects performed experiments were examined using following methods: gene expression profiling microarrays, quantitative polymerase chain reaction (qPCR) enzyme-linked immunosorbent assay (ELISA).Results.The results suggest that ACTH from corticotropes directly indirectly.Indirect most likely occurs interleukin (IL)-6 folliculostellate cells gland.In gland, genes involved immune response.Among them, protein encoded CCL2 seems to also be regulation corticotropin-releasing (CRH)-dependent metabolism.Unlike corticotropic do not react either or Fk866 (the inhibitor Nampt enzymatic action).Conclusions.The indirectly directly, stimulating IL-6 gland.This effect observed cancer line.

Язык: Английский

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