Ontology highlight
ABSTRACT:
PROVIDER: PRJNA940402 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23684843_1.fastq.gz | Fastqsanger.gz | |||
| SRR23684843_2.fastq.gz | Fastqsanger.gz | |||
| SRR23684844_1.fastq.gz | Fastqsanger.gz | |||
| SRR23684844_2.fastq.gz | Fastqsanger.gz | |||
| SRR23684845_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 24 |
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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
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.
2023-03-20 | MSV000091516 | MassIVE
Project description:Characterization of RNA processing events dependent on U2AF-related proteins PUF60 and RBM39. PUF60 (poly-U-binding factor 60 kDa, also known as FIR, Hfp or Ro-bp1) is a splicing factor homologous to the 65 kD subunit of the auxiliary factor of U2 small nuclear ribonucleoprotein (U2AF65). PUF60 has two central RNA recognition motifs and a C-terminal U2AF homology motif (UHM), but lacks the N terminal arginine/serine-rich (RS) and UHM ligand motif (ULM) domains present in U2AF65. PUF60 activity, in conjunction with U2AF, facilitates the association of U2 snRNP with the pre-mRNA. PUF60 and U2AF65 can bind SF3b155 ULMs simultaneously and noncompetitively. RBM39 (also known as CAPERα, HCC1, FSAP59 or RNPC2) is an RNA processing factor and a hormone-dependent transcriptional coactivator. RBM39 domain structure is similar to PUF60, except for the extra N-terminal RS domain with unknown function. To understand function of the two proteins on a genome-wide scale, each protein was individually depleted from human embryonic kidney cell line 293 using RNAi to systematically characterize the PUF60- and RBM39-dependent exon usage.
2018-05-25 | E-MTAB-6010 | biostudies-arrayexpress
Project description:In this study, we showed that activated Wnt/β-catenin signaling suppressed HAL and ARG1, genes associated with cellular metabolism, via CEBPA and FOXA1 transcription factors. In contrast, inhibition of the Wnt signaling pathway increased HAL and ARG1, resulting in decreased intracellular levels of histidine and arginine in liver cancer cells. These data gain an insight into a new role of the Wnt signaling pathway in amino acid metabolism in liver cancer.
2024-03-31 | GSE244527 | GEO
Project description:In this study, we showed that activated Wnt/β-catenin signaling suppressed HAL and ARG1, genes associated with cellular metabolism, via CEBPA and FOXA1 transcription factors. In contrast, inhibition of the Wnt signaling pathway increased HAL and ARG1, resulting in decreased intracellular levels of histidine and arginine in liver cancer cells. These data gain an insight into a new role of the Wnt signaling pathway in amino acid metabolism in liver cancer.
2024-03-31 | GSE244526 | GEO
Project description:In this study, we showed that activated Wnt/β-catenin signaling suppressed HAL and ARG1, genes associated with cellular metabolism, via CEBPA and FOXA1 transcription factors. In contrast, inhibition of the Wnt signaling pathway increased HAL and ARG1, resulting in decreased intracellular levels of histidine and arginine in liver cancer cells. These data gain an insight into a new role of the Wnt signaling pathway in amino acid metabolism in liver cancer.
2024-03-31 | GSE244525 | GEO
Project description:Neuroblastoma is the most common solid tumour in childhood and prognosis remains poor for high-risk cases despite the use of multimodal treatment. Analysis of public drug sensitivity data showed neuroblastoma lines to be particularlysensitive to indisulam, a molecular glue that selectively targets the RNA splicing factor RBM39 for proteosomal degradation via DCAF15-E3-ubiquitin ligase. In neuroblastoma models indisulam induced rapid loss of RBM39, accumulation of splicing errors and growth inhibition in a DCAF15-dependent manner. Integrative analysis of RNAseq and proteomics data highlighted a particular disruption to cell cycle and metabolism. Metabolic profiling demonstrated metabolome perturbations and mitochondrial dysfunction resulting from indisulam. Complete tumour without relapse was observed in both xenografts and the Th-MYCN transgenic model of neuroblastoma after indisulam treatment, with RBM39 loss confirmed in vivo. Our data imply that dual targeting of metabolism and RNA splicing with anti-cancer sulfonamides such as indisulam is promising therapeutic approach for high-risk neuroblastoma.
2022-01-13 | PXD022164 | Pride
Project description:Cancer cell metabolic reprogramming reshapes the tumor microenvironment (TME) into a pro-tumor niche. Arginine metabolism plays complex roles in regulating tumor progression through metabolic cross-feeding among various cell types within the TME, but the primary intercellular communication dominating the collective impact of arginine on tumor progression remains unclear. Here, we investigated the role of arginine metabolism in breast cancer progression using clinical analysis, single-cell RNA sequencing data analysis, and in vivo animal models. We found that the metabolic interplay between cancer cells and macrophages exerts a predominant influence on breast cancer progression mediated by arginine metabolism. Breast cancer cells act as the major source of arginine within the TME, where this tumor-derived arginine fosters a pro-tumor shift in tumor-associated macrophages (TAMs), leading them to suppress the anti-tumor activity of CD8+ T cells. Notably, this cancer cell-macrophage interaction overrides the stimulatory effect of arginine on the anti-tumor capability of CD8+ T cells. Mechanistically, polyamines derived from arginine metabolism mediate TAM polarization via TDG-mediated DNA demethylation, driven by p53 signaling. Importantly, inhibiting the arginine-polyamine-TDG axis across cancer cells to macrophages effectively suppresses breast cancer growth by modulating the immune microenvironment, suggesting therapeutic potential in targeting this axis for breast cancer therapy.
2025-06-30 | GSE285794 | GEO
Project description:RBM39 is a crucial component of the spliceosome that is critical for the integrity of mature mRNA, while depletion of RBM39 by Indisulam significantly increases RNA splicing defects. The antitumor activity of Indisulam is partially attributed to its inhibitory effects on cell cycle progression. To identify the key effector proteins responsible for cell cycle arrest following RBM39 depletion, we employed a multi-omics approach utilizing two chemotypes of RBM39 degraders: Indisulam and CB039. Through proteomics analysis, RNA sequencing, and DepMap cancer cell line dependency analysis, we identified CEP192 as a key gene that exhibited dependency in 96% of 1,100 cancer cell lines. In a panel of eight cancer cell lines, we observed consistent phenotypes upon treatment with CB039 and Indisulam, including skipping of CEP192 exon 42 and downregulation of the CEP192 protein. Mechanistically, treatment with CB039 and Indisulam, as well as CEP192 knockdown via RNA interference, resulted in arrest of cell cycle progression at the G2/M phase. This treatment also induced a disorganized spindle phenotype, as well as condensed and undivided chromosomes. In summary, this work enhances our understanding of the anti-mitotic mechanism underlying RBM39 molecular glue degraders.
2025-03-20 | PXD056341 | Pride
Project description:Indisulam selectively bridges splicing factor RBM39 to DCAF15 for proteasomal degradation. However, clinical trials indicate that patient stratification based upon the mechanism of action of indisulam may be required to achieve the best response. Here we show that neuroblastoma, a MYC-driven cancer characterized by splicing dysregulation, requires RBM39 for survival, expresses high levels of DCAF15 among different solid tumor lineages, and is the most sensitive cancer lineage to indisulam that achieves therapeutic effect by specifically targeting RBM39 in neuroblastoma. Genetic depletion or proteasomal degradation of RBM39 by indisulam induces drastic splicing event changes in neuroblastoma cells. Through specifically targeting RBM39, indisulam induces exceptional tumor response in multiple high-risk neuroblastoma models. Collectively we demonstrate that high RBM39 dependency and high-level expression of DCAF15 provide indisulam a more efficacious therapeutic window to treating high-risk neuroblastoma.
2021-11-24 | GSE164504 | GEO