Cycling back to folate metabolism in cancer

Nature Cancer, Год журнала: 2024, Номер 5(5), С. 701 - 715

Опубликована: Май 2, 2024

Язык: Английский

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The roles and molecular mechanisms of non-coding RNA in cancer metabolic reprogramming

Cancer Cell International, Год журнала: 2024, Номер 24(1)

Опубликована: Янв. 18, 2024

Abstract One of the key features cancer is energy metabolic reprogramming which tightly related to proliferation, invasion, metastasis, and chemotherapy resistance. NcRNAs are a class RNAs having no protein-coding potential mainly include microRNAs, lncRNAs circRNAs. Accumulated evidence has suggested that ncRNAs play an essential role in regulating reprogramming, altered networks mediated by primarily drive carcinogenesis expression enzymes transporter proteins. Importantly, accumulated research revealed dysregulated mediate contributing generation therapeutic tolerance. Elucidating molecular mechanism can provide promising metabolism-related targets for treatment as well overcome In conclusion, this review updates latest mechanisms reprogramming.

Язык: Английский

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Selenium Deficiency Dysregulates One-Carbon Metabolism in Nutritional Muscular Dystrophy of Chicks

Journal of Nutrition, Год журнала: 2022, Номер 153(1), С. 47 - 55

Опубликована: Дек. 20, 2022

Язык: Английский

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Immune checkpoint blockade in pancreatic cancer: Trudging through the immune desert

Seminars in Cancer Biology, Год журнала: 2022, Номер 86, С. 14 - 27

Опубликована: Авг. 27, 2022

Язык: Английский

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Sensitisation of cancer cells to radiotherapy by serine and glycine starvation

British Journal of Cancer, Год журнала: 2022, Номер 127(10), С. 1773 - 1786

Опубликована: Сен. 17, 2022

Abstract Background Cellular metabolism is an integral component of cellular adaptation to stress, playing a pivotal role in the resistance cancer cells various treatment modalities, including radiotherapy. In response radiotherapy, engage antioxidant and DNA repair mechanisms which mitigate remove damage, facilitating cell survival. Given reliance these on amino acid metabolism, we hypothesised that controlling exogenous availability non-essential acids serine glycine would radiosensitise cells. Methods We exposed colorectal, breast pancreatic lines/organoids radiation vitro vivo presence absence glycine. performed phenotypic assays for cycle, ROS levels death, combined with high-resolution untargeted LCMS metabolomics RNA-Seq. Results Serine restriction sensitised range lines, patient-derived organoids syngeneic mouse tumour models Comprehensive metabolomic transcriptomic analysis central carbon revealed impacted not only nucleotide synthesis but had marked inhibitory effect TCA cycle. Conclusion Dietary viable radio-sensitisation strategy cancer.

Язык: Английский

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A prospective prognostic signature for pancreatic adenocarcinoma based on ubiquitination-related mRNA-lncRNA with experimental validation in vitro and vivo

Functional & Integrative Genomics, Год журнала: 2023, Номер 23(3)

Опубликована: Авг. 4, 2023

Ubiquitination-related genes (URGs) exerted a crucial part in variety of human disease disorders; however, their association with pancreatic adenocarcinoma (PAAD) had yet to be clearly described. We aimed comprehensively characterize the contributions URGs PAAD through silico analysis and experimental validation, then identified robust mRNA-lncRNA-based molecular prognostic panel for patients using bulk RNA-sequencing single-cell data. Initially, we collected multi-omics data from TCGA platform depict comprehensive landscape pan-cancer. Furthermore, were accurate in-depth analysis. Significant differences activation ubiquitination pathways expression detected between normal malignant cells. Unsupervised hierarchical clustering determined two subtypes distinct clinical outcomes, pathway activities, immune microenvironment, functional annotation characteristics. The profiles ubiquitination-associated mRNAs lncRNAs training validation datasets utilized develop verify novel ubiquitination-related mRNA-lncRNA panel, which satisfied prediction efficiency. Our model could function as an effective index outperformed four other recognized panels evaluating patients' survival status. Tumor mutation burden, chemotherapy response intensively explored demonstrate underlying mechanism difference according our panel. findings also revealed that FTI-277, farnesyltransferase inhibitor, better curative effect high-risk patients, while MK-2206, Akt allosteric superior therapeutic low-risk patients. real-time PCR results uncovered RNA AC005062.1 all three cell lines was elevated several thousandfold. In conclusion, URGs-based classification triumphantly served tool evaluation PAAD, this developed potential target therapy.

Язык: Английский

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It’s about TIME – Gal-9 as a potential immunotherapeutic target in pancreatic ductal adenocarcinoma

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Янв. 31, 2025

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, characterized by an extremely poor prognosis and limited therapeutic options. Central to progression immune evasion PDAC is tumor (immune) microenvironment (TIME), where checkpoint proteins such as galectin-9 (Gal-9) play pivotal roles. Gal-9 significantly contributes immunosuppressive milieu interacting with various cells, T macrophages, myeloid-derived suppressor cells (MDSCs). These interactions suppress anti-tumor immunity, thus facilitating growth metastasis. This review comprehensively examines multifaceted role in TIME PDAC, detailing its mechanisms action, including induction regulatory polarization tumor-associated modulation apoptotic pathways via Tim-3 caspase activation. The potential targeting Gal-9, either alone or combination other inhibitors anti-PD-L1, also discussed, highlighting preclinical findings that suggest promising avenues for enhancing responses. By elucidating complex biological activities within TIME, this underscores importance innovative strategies aimed at mitigating effects PDAC.

Язык: Английский

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HSP90 Mediates IFNγ-Induced Adaptive Resistance to Anti-PD-1 Immunotherapy

Cancer Research, Год журнала: 2022, Номер 82(10), С. 2003 - 2018

Опубликована: Март 3, 2022

This study reveals an HSP90-centric, iron-modulated mechanism that confers immunosuppression, offering potential therapeutic targets for interfering with acquired resistance to the most prevalent anticancer immunotherapies.

Язык: Английский

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Indoleamine 2,3-dioxygenase 1 in circumventing checkpoint inhibitor responses: Updated

International Immunopharmacology, Год журнала: 2023, Номер 118, С. 110032 - 110032

Опубликована: Март 17, 2023

Язык: Английский

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Phenotypic profiling of solute carriers characterizes serine transport in cancer

Nature Metabolism, Год журнала: 2023, Номер 5(12), С. 2148 - 2168

Опубликована: Дек. 8, 2023

Abstract Serine is a vital amino acid in tumorigenesis. While cells can perform de novo serine synthesis, most transformed rely on uptake to meet their increased biosynthetic requirements. Solute carriers (SLCs), family of transmembrane nutrient transport proteins, are the gatekeepers acquisition and exchange mammalian emerging as anticancer therapeutic targets; however, SLCs that mediate cancer remain unknown. Here we an arrayed RNAi screen SLC-encoding genes while monitoring consumption cell proliferation colorectal using metabolomics high-throughput imaging. We identify SLC6A14 SLC25A15 major cytoplasmic mitochondrial transporters, respectively. also observe SLC12A4 facilitates uptake. Dual targeting either or diminishes growth vitro vivo, particularly with compromised biosynthesis. Our results provide insight into mechanisms contribute intracellular handling.

Язык: Английский

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