Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1208770 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR31982025_1.fastq.gz | Fastqsanger.gz | |||
| SRR31982025_2.fastq.gz | Fastqsanger.gz | |||
| SRR31982026_1.fastq.gz | Fastqsanger.gz | |||
| SRR31982026_2.fastq.gz | Fastqsanger.gz | |||
| SRR31982027_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 12 |
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Project description:Malonyl-CoA, as a key metabolite, is not only the building block for lipogenesis, but also a critical metabolic switcher to mediates flux control over mitochondrial FAs β-oxidation in cellular. However, the levels and entire functions of malonyl-CoA in malignancy and drug resistance is still unclear, especially in those characterized by abnormal lipid metabolism, such as prostate cancer (PCa). Here, we showed the levels of malonyl CoA was increased in PCa, especially in castration-resistant prostate cancer (CRPC). Abnormal accumulation of malonyl-CoA promoted lipogenesis and reprogramed multiple metabolism (including lipid, glucose and amino acid metabolism), sustaining cellular homeostasis to contribute to PCa progression. Restoration of MLYCD expression activated PREK-mediated unfolded protein reaction (UPR) via consuming malonyl-CoA. Importantly, we also found that malonyl-CoA as a donor of malonylation, promoted lysine malonylation in PCa. We identified that malonyl-CoA promoted Ran K141 malonylation, increasing Ran activity and enhancing AR nuclear translocation and transcriptional activity, finally contributing to PCa development and resistance to antiandrogens. These findings highlighted the previously unrecognized role and function of MLYCD-mediated malonyl-CoA in PCa progression via the canonical pathway (metabolic reprogramming) and the non-canonical pathway (malonylated Ran K141), systematically revealing that might be a potentially reliable biomarker and therapy for PCa.
2025-08-21 | PXD060607 | Pride
Project description:Fatty acid beta-oxidation (FAO), the breakdown of lipids, is a metabolic pathway used by various stem cells. FAO levels are generally high during quiescence and downregulated with proliferation. The endogenous metabolite malonyl-CoA modulates lipid metabolism as a reversible FAO inhibitor and as a substrate for de novo lipogenesis. Here we assessed whether malonyl-CoA can be exploited to steer the behavior of hematopoietic stem/progenitor cells (HSPCs), quiescent stem cells of clinical relevance. Treatment of mouse HSPCs in vitro with malonyl-CoA increases HSPC numbers compared to non-treated controls and ameliorates blood reconstitution capacity when transplanted in vivo, mainly through enhanced lymphoid reconstitution. Similarly, human HSPC numbers also increase upon malonyl-CoA treatment in vitro. These data corroborate that lipid metabolism can be targeted to direct cell fate and stem cell proliferation. Physiological modulation of metabolic pathways, rather than genetic or pharmacological inhibition, provides unique perspectives for stem cell manipulations in health and disease.
2020-08-25 | GSE153201 | GEO
Project description:Fundamental alterations in lipid metabolism including increased rates of de novo lipogenesis (DNL), reduced fatty acid oxidation (FAOX) and ectopic lipid accumulation in skeletal muscle and liver are characteristic of type 2 diabetes mellitus (T2DM) and have been hypothesized to directly contribute to the molecular pathogenesis of the disease. Acetyl-CoA carboxylase (ACC) catalyzes the formation of malonyl-CoA, the rate limiting substrate for DML and key regulator of FAOX. ACC inhibitors have the potential to pharmacologically rebalance these metabolic alterations. In the present study, PF-04923503, a potent dual ACC1/ACC2 inhibitor with properties optimized for in vivo studies, suppressed levels of malonyl-CoA in primary hepatocytes, rat skeletal muscle ex vivo, as well as rat liver and skeletal muscle in vivo. This impact on malonyl-CoA was directly correlated (r2>0.9) with reduced hepatic DNL and inversely correlated with incresed rates of FAOX (r2>0.9). The pharmacological eccfect of PF-04923503 persisted with chronic treatment. High-fat fed rats treated with PF-04923503 for six weeks showed dose-dependent reductions in skeletal muscle and liver lipid accumulation. These changes correlated directly with markers for improved insulin sensitization. However, liver gene expression indicates that pharmacological inhibition results in compensation by up-regualtion of genes involved with DNL. These results suggest that pharmacological inhibition of ACC may have utility to help rebalance metabolic abnormalities in T2DM and improve insulin sensitivity. Differential gene expression was assessed by Affymetrix microarray experiments for 15 liver samples across 3 pharmacological treatment groups (vehicle control 0.5% methylcellulose had 5 samples, PF-04923503 10mpk had 5 samples, PF-04923503 30mpk had 5 samples)
2011-06-30 | E-GEOD-28058 | biostudies-arrayexpress
Project description:It is well established that EZH2, a lysine methyltransferase, is upregulated in most of aggressive cancers, highlighting the importance of EZH2 in cancer progression. Recent research has shown that metabolic reprogramming is pivotal in various biological processes, including cancer. Despite this, evidence of EZH2's role in regulating cancer metabolism remains limited. Our study reveals a negative correlation between EZH2 and HMGCS2, a gene belongs to the HMG-CoA synthase, in prostate and breast cancers. Furthermore, HMGCS2 is inversely related to cancer progression and prognosis in these cancers and is epigenetically repressed by EZH2 both in vitro and in vivo. Notably, restored EZH2 reduces the elevated HMGCS2 levels observed upon EZH2 depletion. Overexpression of HMGCS2 decreases tumorigenesis in both prostate and breast cancers. Additionally, β-hydroxybutyrate (BHB), a downstream metabolite of HMGCS2, impedes prostate cancer progression by targeting EZH2 via direct protein-compound interaction -mediated protein degradation. More importantly, ketone drink of BHB administration dramatically reduces tumor size and weight in a prostate cancer xenograft model. Combining ketone drink with FDA-approved drugs enzalutamide and Tazemetostat further suppresses tumor progression. Overall, EZH2- HMGCS2-BHB regulatory network plays a critical role in the progression of prostate cancer and ketone drink is a novel therapeutic tool for patients with aggressive prostate cancer.
2025-05-27 | GSE269208 | GEO
Project description:It is well established that EZH2, a lysine methyltransferase, is upregulated in most of aggressive cancers, highlighting the importance of EZH2 in cancer progression. Recent research has shown that metabolic reprogramming is pivotal in various biological processes, including cancer. Despite this, evidence of EZH2's role in regulating cancer metabolism remains limited. Our study reveals a negative correlation between EZH2 and HMGCS2, a gene belongs to the HMG-CoA synthase, in prostate and breast cancers. Furthermore, HMGCS2 is inversely related to cancer progression and prognosis in these cancers and is epigenetically repressed by EZH2 both in vitro and in vivo. Notably, restored EZH2 reduces the elevated HMGCS2 levels observed upon EZH2 depletion. Overexpression of HMGCS2 decreases tumorigenesis in both prostate and breast cancers. Additionally, β-hydroxybutyrate (BHB), a downstream metabolite of HMGCS2, impedes prostate cancer progression by targeting EZH2 via direct protein-compound interaction -mediated protein degradation. More importantly, ketone drink of BHB administration dramatically reduces tumor size and weight in a prostate cancer xenograft model. Combining ketone drink with FDA-approved drugs enzalutamide and Tazemetostat further suppresses tumor progression. Overall, EZH2- HMGCS2-BHB regulatory network plays a critical role in the progression of prostate cancer and ketone drink is a novel therapeutic tool for patients with aggressive prostate cancer.
2025-05-27 | GSE269259 | GEO
Project description:TFEB promotes prostate cancer progression via regulating ABCA2-dependent lysosomal biogenesis
| PRJNA687482 | ENA
Project description:Fundamental alterations in lipid metabolism including increased rates of de novo lipogenesis (DNL), reduced fatty acid oxidation (FAOX) and ectopic lipid accumulation in skeletal muscle and liver are characteristic of type 2 diabetes mellitus (T2DM) and have been hypothesized to directly contribute to the molecular pathogenesis of the disease. Acetyl-CoA carboxylase (ACC) catalyzes the formation of malonyl-CoA, the rate limiting substrate for DML and key regulator of FAOX. ACC inhibitors have the potential to pharmacologically rebalance these metabolic alterations. In the present study, PF-04923503, a potent dual ACC1/ACC2 inhibitor with properties optimized for in vivo studies, suppressed levels of malonyl-CoA in primary hepatocytes, rat skeletal muscle ex vivo, as well as rat liver and skeletal muscle in vivo. This impact on malonyl-CoA was directly correlated (r2>0.9) with reduced hepatic DNL and inversely correlated with incresed rates of FAOX (r2>0.9). The pharmacological eccfect of PF-04923503 persisted with chronic treatment. High-fat fed rats treated with PF-04923503 for six weeks showed dose-dependent reductions in skeletal muscle and liver lipid accumulation. These changes correlated directly with markers for improved insulin sensitization. However, liver gene expression indicates that pharmacological inhibition results in compensation by up-regualtion of genes involved with DNL. These results suggest that pharmacological inhibition of ACC may have utility to help rebalance metabolic abnormalities in T2DM and improve insulin sensitivity.
2011-06-30 | GSE28058 | GEO
Project description:Mitochondrial fatty acid oxidation (FAO) is an important energy provider for cardiac work and changes in cardiac substrate preference are associated with different heart diseases. Carnitine palmitoyltransferase 1B (CPT1B) is thought to perform the rate limiting enzyme step in FAO and is inhibited by malonyl-CoA. The role of CPT1B in cardiac metabolism has been addressed by inhibiting or decreasing CPT1B protein or after modulation of tissue malonyl-CoA metabolism. We assessed the role of CPT1B malonyl-CoA sensitivity in cardiac metabolism.
2021-04-26 | GSE173256 | GEO
Project description:Mechanisms controlling the proliferative activity of neural stem/progenitor cells (NSPCs) play a pivotal role to ensure life-long neurogenesis in the mammalian brain. How metabolic programs are coupled with NSPC activity remains unknown. Here we show that fatty acid synthase (FASN), the key enzyme of de novo lipogenesis, is highly active in adult NSPCs and that conditional deletion of FASN in NSPCs impairs adult neurogenesis. The rate of de novo lipid synthesis and subsequent proliferation of NSPCs is regulated by Spot14, a gene we found to be selectively expressed in low proliferating adult NSPCs. Spot14 reduces the availability of malonyl-CoA, which is an essential substrate for FASN to fuel lipogenesis. Thus, we here identified a functional coupling between the regulation of lipid metabolism and adult NSPC proliferation. 6 samples were analyzed. Spot14+: Spot14 GFP positive mouse neural stem cell, 3 biological rep Spot14-: Spot14 GFP negative mouse neural stem cell, 3 biological rep
2012-11-02 | E-GEOD-27391 | biostudies-arrayexpress
Project description:The mechanisms underlying cancer metastasis remain poorly understood. Here, we report that TFAM deficiency rapidly and stably induced spontaneous lung metastasis in mice with liver cancer. Interestingly, unexpected polymerization of nuclear actin was observed in TFAM-knockdown HCC cells when cytoskeleton was examined. Polymerization of nuclear actin is causally linked to the high-metastatic ability of HCC cells by modulating chromatin accessibility and coordinating the expression of genes associated with extracellular matrix remodeling, angiogenesis and cell migration. Mechanistically, TFAM deficiency blocked the TCA cycle and increased the intracellular malonyl-CoA levels. Malonylation of mDia2, which drives actin assembly, promotes its nuclear translocation. Importantly, inhibition of malonyl-CoA production or nuclear actin polymerization significantly impeded the spread of HCC cells in mice. Moreover, TFAM was significantly downregulated in metastatic HCC tissues and was associated with overall survival and time to tumor recurrence of HCC patients. Taken together, our study connects mitochondria to the metastasis of human cancer via uncovered mitochondria-to-nucleus retrograde signaling, indicating that TFAM may serve as an effective target to block HCC metastasis.
2024-01-01 | GSE197830 | GEO