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HDAC7 promotes renal cancer metastasis by reprogramming branched-chain amino acid metabolism

ABSTRACT: HDAC7 promotes renal cancer metastasis by reprogramming branched-chain amino acid metabolism

PROVIDER: PRJNA1235210 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR32667188_1.fastq.gz	Fastqsanger.gz
	SRR32667188_2.fastq.gz	Fastqsanger.gz
	SRR32667189_1.fastq.gz	Fastqsanger.gz
	SRR32667189_2.fastq.gz	Fastqsanger.gz
	SRR32667190_1.fastq.gz	Fastqsanger.gz

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HDAC7 promotes renal cancer metastasis by reprogramming branched-chain amino acid metabolism

Project description:Clear cell renal cell carcinoma (ccRCC), the most common subtype of kidney cancer, exhibits significant metabolic reprogramming. We previously reported elevated HDAC7, a class II histone deacetylase, in ccRCC. Here, we demonstrate that HDAC7 promotes aggressive phenotypes and in vivo tumor progression in RCC. HDAC7 suppresses the expression of genes mediating branched-chain amino acid (BCAA) catabolism. Notably, lower expression of BCAA catabolism genes is strongly associated with worsened survival in ccRCC. Suppression of BCAA catabolism promotes expression of SNAIL1, a central mediator of aggressive phenotypes including migration and invasion. HDAC7-mediated suppression of the BCAA catabolic program promotes SNAI1 mRNA transcription via NOTCH signaling activation. Collectively, our findings provide new insights into the role of metabolic remodeling in ccRCC tumor progression.

2025-03-20 | GSE291765 | GEO

Impact of Preoperative Oral Branched-chain Amino Acids on Reducing Postoperative Insulin Resistance.

Project description:Postoperative insulin resistance refers to the phenomenon that the body’s glucose uptake stimulated by insulin is reduced due to stress effects such as trauma or the inhibitory effect of insulin on liver glucose output is weakened after surgery. There is a clear link between postoperative insulin resistance and poor perioperative prognosis. Therefore, exploring interventions to reduce postoperative stress insulin resistance, stabilize postoperative blood glucose, and reduce postoperative complications are clinical problems that need to be solved urgently. In recent years, research on branched-chain amino acids and metabolic diseases has become a hot spot. Studies have found that in the rat model, preoperatively given a high branched-chain amino acid diet can inhibit postoperative insulin resistance and stabilize blood glucose levels. This research plan is to try to add branched-chain amino acids before surgery to observe the occurrence of postoperative insulin resistance in patients.

| 2744698 | ecrin-mdr-crc

Reprograming of Proteasomal Degradation by Branched Chain Amino Acid Metabolism

Project description:Reprograming of Proteasomal Degradation by Branched Chain Amino Acid Metabolism

| PRJNA769111 | ENA

Nervous system reduction in branched-chain amino acid metabolism disrupts hippocampal neurogenesis and memory

Project description:To study the role of branched-chain amino acid metabolism in neural stem cells we generated two primary neural stem cell culture lines in which on was deleted for the Ppm1k gene using floxed cells and adenovirus delviered cre-recombinase.

2023-04-06 | GSE205603 | GEO

Dynamic partitioning of branched-chain amino acids- derived nitrogen supports renal cancer progression

Project description:Metabolic reprogramming is critical for tumor initiation and progression. However, the exact impact of specific metabolic changes on cancer progression is poorly understood. Here, we integrate multimodal analyses of primary and metastatic clonally-related clear cell renal cancer cells (ccRCC) grown in physiological media to identify key stage-specific metabolic vulnerabilities. We show that a VHL loss-dependent reprogramming of branched-chain amino acid catabolism sustains the de novo biosynthesis of aspartate and arginine enabling tumor cells with the flexibility of partitioning the nitrogen of the amino acids depending on their needs. Importantly, we identify the epigenetic reactivation of argininosuccinate synthase (ASS1), a urea cycle enzyme suppressed in primary ccRCC, as a crucial event for metastatic renal cancer cells to acquire the capability to generate arginine, invade in vitro and metastasize in vivo. Overall, our study uncovers a mechanism of metabolic flexibility occurring during ccRCC progression, paving the way for the development of novel stage-specific therapies.

2022-11-10 | GSE217211 | GEO

Reprograming of Proteasomal Degradation by Branched Chain Amino Acid Metabolism

Project description:Branched‐chain amino acid (BCAA) metabolism is a central hub for energy production and regulation of numerous physiological processes. Controversially, both increased and decreased levels of BCAAs are associated with longevity. Using genetics and multi‐omics analyses in Caenorhabditis elegans, we identified adaptive regulation of the ubiquitin‐proteasome system (UPS) in response to defective BCAA catabolic reactions after the initial transamination step. Worms with impaired BCAA metabolism show a slower turnover of a GFP‐based proteasome substrate, which is suppressed by loss‐of‐function of the first BCAA catabolic enzyme, the branched‐chain aminotransferase BCAT‐1. The exogenous supply of BCAA‐derived carboxylic acids, which are known to accumulate in the body fluid of patients with BCAA metabolic disorders, is sufficient to regulate the UPS. The link between BCAA intermediates and UPS function presented here sheds light on the unexplained role of BCAAs in the aging process and opens future possibilities for therapeutic interventions.

2022-09-22 | GSE185451 | GEO

Dynamic partitioning of branched-chain amino acids- derived nitrogen supports renal cancer progression

Project description:Dynamic partitioning of branched-chain amino acids- derived nitrogen supports renal cancer progression

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Drosophila miR-277 controls branched-chain amino acid catabolism and affects lifespan

Project description:Development, growth and adult survival are coordinated with available metabolic resources. The insulin/IGF and TOR signaling pathways relay nutritional status, thereby ascertaining that the organism responds appropriately to environmental conditions. MicroRNAs are short (21-23 nt) regulatory RNAs that confer specificity on the RNA-induced silencing complex (RISC) to inhibit a given set of mRNA targets. We profiled changes in miRNA expression during adult life in Drosophila melanogaster and determined that miR-277 is down-regulated with age. This miRNA controls branched-chain amino acid (BCAA) catabolism and the activity of the TOR kinase, a central growth regulator. Metabolite analysis suggests that the mechanistic basis may be an accumulation of BCKAs, rather than BCAAs, thus avoiding potentially detrimental consequences of increased branched chain amino acid levels on e.g. translational fidelity. Constitutive miR-277 expression as well as transgenic inhibition with a miRNA sponge construct shortens lifespan. Furthermore, constitutive miR-277 expression is synthetically lethal with reduced insulin signaling. Thus, optimal metabolic adaptation requires tuning of cellular BCAA catabolism by miR-277 to be concordant with systemic growth signaling.

2015-01-19 | GSE42442 | GEO

The Effect of Branched Chain Amino Acid to the Perioperative Nutritional Status: In Patients with Cirrhosis Undergoing Liver Resection and Patients Awaiting Liver Transplantation.

Project description:Interventions: Patients assigned for intervention group take Branched-chain amino acid formula as late-evening snack for 2 weeks preoperatively in hepatic resction,and for 4 weeks in liver transplantation,respectively. Administration of BCAA formula would be maintained for 12 weeks postoperatively in both procedure. Patients in the control group are observed without administration of BCAA formula. Primary outcome(s): Body cell mass Study Design: Parallel Non-randomized

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Mitochondrial Calcium Signaling Regulates Branched-Chain Amino Acid Catabolism in Fibrolamellar Carcinoma

Project description:Mitochondrial Calcium Signaling Regulates Branched-Chain Amino Acid Catabolism in Fibrolamellar Carcinoma

| PRJNA1234606 | ENA