Similar Datasets
Project description:To assess the role of BCAT1 in uveal melanoma chemotherapy resistance, we utilized lentivirus packaged shBCAT1 to knockdown in UM resistant cell lines.
2026-05-31 | GSE333261 | GEO
Project description:To study the mechanism of cisplatin resistance in uveal melanoma, we performed RNA-seq of 92.1-parental and 92.1-resistant uveal melanoma cells.
2026-01-01 | GSE271497 | GEO
Project description:To study the mechanism of cisplatin resistance in uveal melanoma, we performed H3K9ac and H3K27ac Cut&Tag in 92.1-parental and 92.1-resistant uveal melanoma cells.
2026-01-01 | GSE271539 | GEO
Project description:The role of lncRNA in uveal melanoma (UM) is not well studied. We used microarrays to identify the downstream targets of MAT1 lncRNA to invesitgate the mechanism of lncRNA in UM oncogenesis
2022-03-31 | GSE199554 | GEO
Project description:The branched chain amino acid (BCAA) pathway and high levels of BCAA transaminase 1 (BCAT1) have recently been associated with aggressiveness in several cancer entities. However, the mechanistic role of BCAT1 in this process remains largely uncertain. By performing high-resolution proteomic analysis of human acute myeloid leukaemia (AML) stem cell (LSC) and non-LSC populations, we found the BCAA pathway enriched and BCAT1 overexpressed in LSCs. We show that BCAT1, which transfers α-amino groups from BCAAs to α-ketoglutarate (αKG), is a critical regulator of intracellular αKG homeostasis. Next to its role in the tricarboxylic acid (TCA) cycle αKG is an essential co-factor for αKG-dependent dioxygenases such as EGLN1 and the TET family of DNA demethylases. Knockdown of BCAT1 in leukaemia cells caused accumulation of αKG leading to HIF1a protein degradation mediated by EGLN1. This resulted in a growth and survival defect and abrogated leukaemia-initiating potential. In contrast, overexpression (OE) of BCAT1 in leukaemia cells decreased intracellular αKG levels and caused DNA hypermethylation via altered TET activity. BCAT1high AMLs displayed a DNA hypermethylation phenotype similar to cases carrying mutant isocitrate dehydrogenase (IDHmut), in which TET2 is inhibited by the oncometabolite 2-hydroxyglutarate. High levels of BCAT1 strongly correlate with shorter overall survival in IDHwtTET2wt, but not IDHmut or TET2mut AMLs. Gene sets characteristic for IDHmut AMLs were enriched in IDHwtTETwtBCAT1high patient samples. BCAT1high AMLs showed robust enrichment for LSC signatures and paired sample analysis revealed a significant increase of BCAT1 levels upon disease relapse. In summary, by limiting intracellular αKG, BCAT1 links BCAA catabolism to HIF1a stability and regulation of the epigenomic landscape. Our results suggest the BCAA-BCAT1-αKG pathway as a therapeutic target to compromise LSC function in IDHwtTET2wt AML patients.
2017-11-08 | GSE100778 | GEO
Project description:The branched chain amino acid (BCAA) pathway and high levels of BCAA transaminase 1 (BCAT1) have recently been associated with aggressiveness in several cancer entities. However, the mechanistic role of BCAT1 in this process remains largely uncertain. By performing high-resolution proteomic analysis of human acute myeloid leukaemia (AML) stem cell (LSC) and non-LSC populations, we found the BCAA pathway enriched and BCAT1 overexpressed in LSCs. We show that BCAT1, which transfers α-amino groups from BCAAs to α-ketoglutarate (αKG), is a critical regulator of intracellular αKG homeostasis. Next to its role in the tricarboxylic acid (TCA) cycle αKG is an essential co-factor for αKG-dependent dioxygenases such as EGLN1 and the TET family of DNA demethylases. Knockdown of BCAT1 in leukaemia cells caused accumulation of αKG leading to HIF1a protein degradation mediated by EGLN1. This resulted in a growth and survival defect and abrogated leukaemia-initiating potential. In contrast, overexpression (OE) of BCAT1 in leukaemia cells decreased intracellular αKG levels and caused DNA hypermethylation via altered TET activity. BCAT1high AMLs displayed a DNA hypermethylation phenotype similar to cases carrying mutant isocitrate dehydrogenase (IDHmut), in which TET2 is inhibited by the oncometabolite 2-hydroxyglutarate. High levels of BCAT1 strongly correlate with shorter overall survival in IDHwtTET2wt, but not IDHmut or TET2mut AMLs. Gene sets characteristic for IDHmut AMLs were enriched in IDHwtTETwtBCAT1high patient samples. BCAT1high AMLs showed robust enrichment for LSC signatures and paired sample analysis revealed a significant increase of BCAT1 levels upon disease relapse. In summary, by limiting intracellular αKG, BCAT1 links BCAA catabolism to HIF1a stability and regulation of the epigenomic landscape. Our results suggest the BCAA-BCAT1-αKG pathway as a therapeutic target to compromise LSC function in IDHwtTET2wt AML patients.
2017-11-08 | GSE103960 | GEO
Project description:The function and mechanism of lncRNA in human uveal melanoma (UM) is not clearly studied. We used microarrays to identify the downstream target genes of CANT1 lncRNA in UM cells to explain the mechanism of lncRNA in UM tumorigenesis
2017-01-16 | GSE71161 | GEO
Project description:Transcriptome analysis of 92.1-parental and 92.1-resistant uveal melanoma cells
| PRJNA1131825 | ENA
Project description:Previously, we have identified cytosolic form of the branched chain amino-acid transaminase 1 (BCAT1) as notably hypomethylated in low-malignant potential (LMP) and high-grade (HG) serous epithelial ovarian tumors, compared to normal ovarian tissues. Here we show that BCAT1 is strongly overexpressed in both LMP and HG serous EOC tumors, thus suggesting that epigenetic mechanisms might be implicated in BCAT1 overexpression in serous epithelial ovarian cancer (EOC). Knockdown of the BCAT1 expression in EOC cells led to sharp decrease of cell proliferation and induced S-phase cell cycle arrest. Additionally, BCAT1 suppression significantly inhibited EOC cell migration and invasion. Gene expression profiling and consecutive network and pathway analyses confirmed these findings, as numerous genes and pathways known previously to be implicated in ovarian tumorigenesis, including EOC tumor invasion and metastasis, were found to be downregulated upon BCAT1 suppression, while some tumor suppressor genes were induced. Taken together, our data are indicative for a strong oncogenic potential of the BCAT1 gene in advanced EOC and identify this transaminase as a novel EOC biomarker and putative EOC therapeutic target.
2015-10-01 | GSE64424 | GEO
Project description:To investigate the mechanism of BCAT1 in mediating resistance to third-generation EGFR-TKI, we employed RNA-seq analysis to compare the transcriptome signature of ASK120067-resistant NSCLC cells with or without BCAT1 knockdown. Here, gene set enrichment (GSEA) revealed a significant decrease in the expression of genes in glycolysis pathway following small interfering RNA (siRNA)-mediated BCAT1 knockdown, which indicated the role for BCAT1 in supporting TKI resistance through upregulation of glycolysis.
2024-08-15 | GSE247584 | GEO