Cancer-associated fibroblast-derived urea cycle metabolites promote colorectal cancer growth
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PROVIDER: PRJNA1203894 | ENA |
REPOSITORIES: ENA
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Project description:Urea cycle (UC) dysfunction is linked to both tumorigenesis and poor prognosis in multiple cancers. However, the role of UC metabolism in tumor-stroma crosstalk is unclear. Here, we show that colorectal cancer (CRC) cells induce reprogramming of UC metabolism in cancer-associated fibroblasts (CAFs), which is mediated by CRC-derived exosomes. Reprogrammed CAFs support CRC cell growth by providing UC metabolites, especially arginine (Arg). Consequently, Arg deprivation resulted in growth inhibition of CRC cells. Furthermore, we found that Arg deprivation increases CRC’s dependence on putrescine (Put) and upregulates the expression of the polyamine biosynthetic rate-limiting enzyme ornithine decarboxylase (ODC). Combined Arg deprivation and ODC inhibitor effectively restrains CRC cell growth. Our study illustrates the UC metabolic interaction between CAFs and CRC cells and demonstrates the potential therapeutic utility of Arg restriction and ODC blockade combination treatment for colorectal cancer.
2025-01-31 | GSE285472 | GEO
Project description:We investigate the role of urea cycle dysregulation on cancer genome by perturbing the UC enzymes (over expression or knock-down) in different cancer cell lines.
| PRJEB27646 | ENA
Project description:Purpose: Nuclear Factor I B (NFIB) has been reported to promote tumor growth, metastasis, and liver regeneration, but its mechanism in liver cancer is not fully elucidated. The present study aims to reveal the role of NFIB in hepatocellular carcinogenesis Methods:In our study, we constructed hepatocyte-specific NFIB gene knockout mice with CRISPR/Cas9 technology (Nfib-/-; Alb-cre), and induced liver cancer mouse model by intraperitoneal injection of DEN/CCl4 Results: First, we found that Nfib-/-; Alb-cre mice developed more tumor nodules and had heavier livers than wild-type mice. H&E staining indicated that the liver histological severity of Nfib-/- group was more serious than that of WT group. Then we found that the differentially expressed genes in the tumor tissue between Nfib-/- mice and wild type mice were enriched in urea cycle. Furthermore, ASS1 and CPS1, the core enzymes of the urea cycle, were significantly upregulated in Nfib-/- tumors. Subsequently, we validated that the expression of ASS1 and CPS1 increased after knockdown of NFIB by lentivirus in normal hepatocytes and also promoted cell proliferation in vitro. In addition, ChIP assay confirmed that NFIB can bind with promoter region of both ASS1 and CPS1 gene Conclusions:Our study reveals for the first time that hepatocyte-specific knock-out of Nfib aggravates hepatocellular tumor development by enhancing the urea cycle.
2022-06-23 | GSE200708 | GEO
Project description:Urea cycle disorders with hyperammonemia remain difficult to treat and eventually necessitate liver transplantation. An ornithine transcarbamylase defect (Otcspf-ash) mouse model, a model of urea cycle disorder, was used to test whether knockdown of a key glutamine metabolism enzyme glutaminase 2 (Gls2) or glutamine dehydrogenase 1 (Glud1) could rescue the hyperammonemia and associated lethality induced by a high protein diet. Reduced hepatic expression of Gls2, but not Glud1, by AAV8-mediated delivery of a short hairpin RNA in Otcspf-ash mice diminished hyperammonemia, reduced body weight loss, and reduced lethality. These data suggest that Gls2 hepatic knockdown could help alleviate risk for hyperammonemia and other clinical manifestations of patients suffering from defects in the urea cycle.
2022-06-07 | GSE179342 | GEO
Project description:Single cell sequencing to investigate the alteration of urea cycle in DFMO treated mouse
2024-05-29 | GSE175805 | GEO
Project description:ra05-09_urea - urea - What are the transcriptomic plant responses to urea nitrogen supply ? - Columbia Arabidopsis ecotype were grown hydroponically on 0.5 mM NH4NO3 as sole nitrogen source during 35 days under short days. Plants were then placed on 3 nutrient solutions supplemented, either with 1 mM NH4NO3, or with 0.5 mM NH4NO3 + 0.5 mM Urea, or with 1 mM Urea. Root and shoot samples were harvested separately 7 days after these different nitrogen treatments Keywords: treated vs untreated comparison
2007-10-16 | GSE9258 | GEO
Project description:Excess/residual urea is a pervasion problem in wine and Sake fermentation. We sought to reduce residual urea levels (to reduce ethyl carbamate leves) by engineering the Sake yeast strain K7 to constitutively express either the urea amidolyase (Dur1,2) or urea importer (Dur3). We sought to then compare the gene expression profiles of the metabolically engineered yeast strains to the parental strain during fermentation. Engineered strains would hopefully have gene expression profiles that were minimally different from the parental strain.
2010-04-21 | GSE17867 | GEO
Project description:Despite it being the most common incident of cancer among men, the pathophysiological mechanisms contributing to prostate cancer (PCa) are still poorly understood. Altered mitochondrial metabolism is postulated to play a role in the development of PCa. To determine the key metabolites (which included mitochondrial oncometabolites), benign prostatic and cancer tissues of patients with PCa were analyzed using capillary electrophoresis and liquid chromatography coupled with mass spectrometry. Gene expression was studied using real-time PCR. In PCa tissues, we found reduced levels of early tricarboxylic acid cycle metabolites, whereas the contents of urea cycle metabolites including aspartate, argininosuccinate, arginine, proline, and the oncometabolite fumarate were higher than that in benign controls. Fumarate content correlated positively with the gene expression of oncogenic HIF1α and NFκB pathways, which were significantly higher in the PCa samples than in the benign controls. Furthermore, data from the TCGA database demonstrated that prostate cancer patients with activated NFκB pathway had a lower survival rate. In summary, our data showed that fumarate content was positively associated with carcinogenic genes.
| S-EPMC7408908 | biostudies-literature
Project description:Longitudinal Study of Urea Cycle Disorders - UCDC 5101
| PRJNA185155 | ENA
Project description:Excess/residual urea is a pervasion problem in wine and Sake fermentation. We sought to reduce residual urea levels (to reduce ethyl carbamate leves) by engineering the Sake yeast strain K7 to constitutively express either the urea amidolyase (Dur1,2) or urea importer (Dur3). We sought to then compare the gene expression profiles of the metabolically engineered yeast strains to the parental strain during fermentation. Engineered strains would hopefully have gene expression profiles that were minimally different from the parental strain. Yeast strains were used to ferment Chardonnay grape must and total RNA harvested at 24 hrs into fermentation. 10 ug of total RNA was made into cDNA, and then labelled cRNA, with the Affymetrix GeneChip one cycle target amplification and labelling system. Fragmented cRNA was then hybridized to an Affymetrix YGS98 array in biological duplicate.
2010-05-07 | E-GEOD-17867 | biostudies-arrayexpress