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Arginine reprograms metabolism in liver cancer via RBM39

ABSTRACT: Metabolic reprogramming is a hallmark of cancer. However, mechanisms underlying metabolic reprogramming and how altered metabolism in turn enhances tumorigenicity are poorly understood. Here, we report that arginine levels are elevated in hepatocellular carcinoma (HCC) despite reduced expression of arginine synthesis genes, in murine and patient tumors. Tumor cells accumulate high levels of arginine due to increased uptake and reduced arginine-to-polyamine conversion. Importantly, the high levels of arginine promote tumor formation via further metabolic reprogramming, including changes in glucose, amino acid, nucleotide, and fatty acid metabolism. Mechanistically, arginine binds RNA-binding motif protein 39 (RBM39) to control expression of metabolic genes. RBM39-mediated upregulation of asparagine synthesis leads to enhanced arginine uptake, creating a positive feedback loop to sustain high arginine levels and oncogenic metabolism. Thus, arginine is a second messenger-like molecule that reprograms metabolism to promote tumor growth.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (ncbitaxon:9606) Mus Musculus (ncbitaxon:10090)

SUBMITTER: Alexander Schmidt

PROVIDER: MSV000091516 | MassIVE | Mon Mar 20 23:12:00 GMT 2023

SECONDARY ACCESSION(S): PXD040995

REPOSITORIES: MassIVE

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Arginine reprograms metabolism in liver cancer via RBM39 [AA_overexpression/RBM39depletion]

Project description:Metabolic reprogramming is a hallmark of cancer. However, mechanisms underlying metabolic reprogramming and how altered metabolism in turn enhances tumorigenicity are poorly understood. Here, we report that arginine levels are elevated in hepatocellular carcinoma (HCC) despite reduced expression of arginine synthesis genes, in murine and patient tumors. Tumor cells accumulate high levels of arginine due to increased uptake and reduced arginine-to-polyamine conversion. Importantly, the high levels of arginine promote tumor formation via further metabolic reprogramming, including changes in glucose, amino acid, nucleotide, and fatty acid metabolism. Mechanistically, arginine binds RNA-binding motif protein 39 (RBM39) to control expression of metabolic genes. RBM39-mediated upregulation of asparagine synthesis leads to enhanced arginine uptake, creating a positive feedback loop to sustain high arginine levels and oncogenic metabolism. Thus, arginine is a second messenger-like molecule that reprograms metabolism to promote tumor growth.

2023-12-24 | GSE227106 | GEO

Targeting Pyrimidine Synthesis Accentuates Molecular Therapy Response in Glioblastoma Stem Cells

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H3K27ac ChIP-seq BTIC vs. DGC

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Systems level profiling of arginine starvation in ASS1 negative sarcomas reveals ERK and MYC adaptive metabolic reprogramming of TCA anaplerosis and lipid metabolism

Project description:submission for the paper "Systems level profiling of arginine starvation in ASS1 negative sarcomas reveals ERK and MYC adaptive metabolic reprogramming of TCA anaplerosis and lipid metabolism"

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Transcriptome analysis of Pseudomonas aeruginosa PAO1 Response to L-Glutamate or D-Arginine

Project description:Arginine utilization in Pseudomonas aeruginosa with multiple catabolic pathways represents one of the best examples of metabolic versatility of this organism. To identify genes of this complex arginine network, we employed DNA microarray to analyze the transcriptional profiles of this organism in response to L-arginine. While most genes in arginine uptake, regulation and metabolism have been identified as members of the ArgR regulon in our previous study, eighteen putative transcriptional units of 38 genes including the two known genes of the arginine dehydrogenase (ADH) pathway, kauB and gbuA, were found inducible by exogenous L-arginine but independent of ArgR. We conducted three independent microarray experiments in the presence (experimental) of L-Glutamate or D-Arginine. P. aeruginosa PAO1 was grown aerobically in minimal medium P with 300 rpm shaking at 37Â°C, in the presence of L-Glu with or without the addition of D-Arg at 20 mM.

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Transcriptome analysis of Pseudomonas aeruginosa PAO1 Response to L-Glutamate or D-Arginine

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