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Methionine Restriction Reduces Lung Cancer Progression and Increases Chemotherapy Response

ABSTRACT: Methionine Restriction Reduces Lung Cancer Progression and Increases Chemotherapy Response

PROVIDER: PRJNA1126222 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR29477331_1.fastq.gz	Fastqsanger.gz
	SRR29477331_2.fastq.gz	Fastqsanger.gz
	SRR29477332_1.fastq.gz	Fastqsanger.gz
	SRR29477332_2.fastq.gz	Fastqsanger.gz
	SRR29477333_1.fastq.gz	Fastqsanger.gz

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Methionine Restriction Reduces Lung Cancer Progression and Increases Chemotherapy Response

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Effects of 20 months Dietary Methionine Restriction on Hepatic Gene Expression in Fischer 344 Rats

Project description:Dietary methionine restriction (MR) has been shown to increase lifespan and decrease adiposity in rodents. This study was designed to examine the transcriptional effects of MR in metabolically relevant tissues. This experiment contains data from the liver. We analyzed MR-induced changes in gene expression using pooled RNA from liver of rats fed either a control purified amino acid diet (DL-methionine content of 0.86%) (CON) or a methionine-restricted diet (DL-methionine content of 0.172%)(MR). Rats were fed Purina rodent diet 5001 until 32 days of age and were then randomly assigned to be fed CON diet or MR diet for 20 months.

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The opposing impacts of dietary methionine restriction on tumor growth in immunodeficient and immunocompetent mice

Project description:Methionine, a sulfur-containing essential amino acid, is a key component of dietary proteins important for protein synthesis, sulfur metabolism, antioxidant defense, and signaling. However, the role of methionine in cancer progression remains inconclusive. On one hand, dietary methionine restriction is known to repress cancer growth and improve cancer therapy in xenografted tumors. On the other hand, methionine is also critical for T cell activation and differentiation, making it a potential tumor suppression nutrient by enhancing T cell-mediated anti-tumor immunity. Here we investigated the interaction between dietary methionine, immune cells, and cancer cells by allografting CT26.WT mouse colon carcinoma cells into immunocompetent Balb/c mice or immunodeficient NSG mice, then analyzed how dietary methionine contents affect their growth. Our results show that dietary methionine restriction suppresses tumor growth in immunodeficient NSG mice but promotes tumor progression in immunocompetentt Balb/c mice.

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Genome-wide map of H3K4me3 before and after methionine restriction in HCT116 cells.

Project description:The goals of this study were to compare the distribution of H3K4me3 before and after methionine restriction to understand how nutrient availability and alterations in methionine metabolism affect the epigenetic state and regulate gene transcription. To do this we performed ChIP-seq with an H3K4me3 antibody and RNA-seq using PolyA+ mRNA.

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Project description:Dietary methionine restriction represses growth and improves therapeutic responses in several pre-clinical settings. However, how this dietary intervention impacts cancer progression in the context of the immune system is unknown. Here we analyzed the CD45+ immune cells from the small intestine of control (CTRL) diet or methionine-restricted (MR) diet fed tumor-free C57BL/6J donor mice and tumor-bearing Apc <min+/-> recipient mice transplanated with feces from these diet-fed tumor-free C57BL/6J mice by scRNA-seq. Our analysis indicate that fecal microbes from methionine-restricted tumor-free C57BL/6J mice are sufficient to represss T cell activation in the small intestine of Apc <min+/-> mice.

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Project description:The goal of this study was to compare next-generation sequencing (NGS)-derived liver and pectoralis major transcriptome profilings (RNA-seq) of chicken fed control diet to treatment birds fed methionine restriction diet. We sequenced mRNA from 10 Gallus gallus males fed either control (L-Methionine) or L-Methionine-deficient diet (5 control and 5 treatment) from 3-5 weeks of age. We sequenced both liver and the pectoralis major muscle.

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Recurrent application of dietary restriction reduces tumor load and increases lifespan in an intestinal cancer model

Project description:Recurrent application of dietary restriction reduces tumor load and increases lifespan in an intestinal cancer model

| PRJNA555314 | ENA

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Project description:Dietary methionine restriction (MR) has been shown to increase lifespan and decrease adiposity in rodents. This study was designed to examine the transcriptional effects of MR in metabolically relevant tissues. This experiment contains data from the inguinal white adipose tissue (IWAT). We analyzed MR-induced changes in gene expression using pooled RNA from IWAT of rats fed either a control purified amino acid diet (DL-methionine content of 0.86%) (CON) or a methionine-restricted diet (DL-methionine content of 0.172%)(MR). Rats were fed Purina rodent diet 5001 until 32 days of age and were then randomly assigned to be fed CON diet or MR diet for 20 months.

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Project description:Epigenetic modifications on DNA and histones regulate gene expression by modulating chromatin accessibility to transcription machinery. Chromatin-modifying enzymes are dependent on metabolic intermediates for chromatin remodeling, linking nutrient availability and cellular metabolism to the cellular epigenetic landscape. Here we identify methionine as a key nutrient affecting T cell epigenetic reprogramming in CD4+ T helper (Th) cells. Using metabolomic approaches, we showed that methionine is rapidly taken up by activated T cells and then serves as the major substrate for the biosynthesis of S-adenosyl-L-methionine (SAM), the universal methyl donor for cellular methyltransferases. Conversely, methionine restriction (MR) depletes intracellular SAM pools, reduces global histone H3K4 methylation (H3K4me3) in T cells, and reduces H3K4me3 levels at the promoter regions of key genes involved in CD4+ Th17 cell proliferation and cytokine production. Applied to the mouse model of multiple sclerosis (experimental autoimmune encephalomyelitis), dietary methionine restriction reduced the expansion of pathogenic Th17 cells in vivo, leading to reduced T cell-mediated neuroinflammation and disease onset. Overall our data identify methionine as a key nutritional factor that shapes T cell proliferation, differentiation, and function in part through regulation of histone methylation in T cells.

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