The effect of UXS1 or MRPL42 on the mRNA expression in hepatocellular carcinoma cell line HCCLM3
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE310304 | GEO | 2026/05/31
REPOSITORIES: GEO
Similar Datasets
Project description:Kelch-like ECH associated protein 1 (KEAP1) is the third most commonly mutated gene in non-small cell lung cancer (NSCLC) and is associated with poor prognosis. Here, we investigated synthetic lethal interaction genes in KEAP1-mutated cancer cells and identified a dependency on UDP xylose synthase 1 (UXS1), which converts UDP-glucuronic acid (UDP-GlcA) to UDP- xylose in the proteoglycan synthetic pathway. UDP glucose dehydrogenase (UGDH), a transcriptional target of NRF2 that converts UDP-glucose to UDP-GlcA, was highly expressed in KEAP1-mutant tumors. Upon UXS1 knockdown, depletion of UDP-xylose occurred in both KEAP1-mutant and wildtype (WT) cells, whereas UDP-GlcA accumulated to a greater extent in the KEAP1-mutant setting. The resulting shortage of available UDP and other pyrimidines slowed S-phase progression and stalled DNA replication fork marks, causing cells to undergo prolonged cell-cycle exit or apoptosis. Dependency on UXS1 was rescued by knocking out UGDH to prevent UDP-GlcA accumulation and UDP depletion. DNA replication stress in UXS1-depleted cells sensitized them to clinical cell-cycle checkpoint inhibitors. Further, CRISPR screening experiments identified genes that modulate UXS1 dependency. While liver had the highest normal tissue expression of UGDH, UXS1 knockout in the liver did not result in hepatotoxicity. Taken together, these data demonstrate that UXS1 is a selective dependency in KEAP1-mutant tumors and loss of UXS1 creates additional therapeutically exploitable vulnerabilities in KEAP1-mutant tumors.
2025-08-20 | GSE305124 | GEO
Project description:Kelch-like ECH associated protein 1 (KEAP1) is the third most commonly mutated gene in non-small cell lung cancer (NSCLC) and is associated with poor prognosis. Here, we investigated synthetic lethal interaction genes in KEAP1-mutated cancer cells and identified a dependency on UDP xylose synthase 1 (UXS1), which converts UDP-glucuronic acid (UDP-GlcA) to UDP- xylose in the proteoglycan synthetic pathway. UDP glucose dehydrogenase (UGDH), a transcriptional target of NRF2 that converts UDP-glucose to UDP-GlcA, was highly expressed in KEAP1-mutant tumors. Upon UXS1 knockdown, depletion of UDP-xylose occurred in both KEAP1-mutant and wildtype (WT) cells, whereas UDP-GlcA accumulated to a greater extent in the KEAP1-mutant setting. The resulting shortage of available UDP and other pyrimidines slowed S-phase progression and stalled DNA replication fork marks, causing cells to undergo prolonged cell-cycle exit or apoptosis. Dependency on UXS1 was rescued by knocking out UGDH to prevent UDP-GlcA accumulation and UDP depletion. DNA replication stress in UXS1-depleted cells sensitized them to clinical cell-cycle checkpoint inhibitors. Further, CRISPR screening experiments identified genes that modulate UXS1 dependency. While liver had the highest normal tissue expression of UGDH, UXS1 knockout in the liver did not result in hepatotoxicity. Taken together, these data demonstrate that UXS1 is a selective dependency in KEAP1-mutant tumors and loss of UXS1 creates additional therapeutically exploitable vulnerabilities in KEAP1-mutant tumors.
2025-08-20 | GSE304915 | GEO
Project description:UDP-glucuronic acid (UDP-GlcUA) is a nucleotide sugar that plays important roles in many organisms and excessive UDP-GlcUA in the cell causes many defects in the cellular processes. In Cryptococcus spp., mutations in the UXS1 gene which encodes an enzyme that converts UDP-GlcUA into UDP-xylose trigger high level accumulation of UDP-GlcUA and effectuate resistance to the antifungal drug 5-fluorocytosine. Here, we show that elevation of UDP-GlcUA affects several cellular processes including growth rate, ability to grow at various stress conditions, and resistance to fluorine containing analogs. RNA-seq analyses reveal that UXS1 deletion leads to the identification of three differentially expressed endopeptidase genes, notably PEP401. Lack of PEP401 from the uxs1 mutant background reduces the UDP-GlcUA levels and reverts all the phenotypes of the uxs1 mutant toward the wild-type characteristics. Particularly, high levels of UDP-GlcUA not only regulate expression of PEP401 at RNA and protein levels, but it also enhances the proteolytic activity of total protein extracts in a PEP401-dependent manner, establishing a functional link between nucleotide sugar metabolism and proteolytic regulation. Moreover, the UDP-GlcUA transporter gene, UUT1, can further modulate the levels of UDP-GlcUA in the uxs1 pep401 double mutant and manifests the drug resistance phenotypes observed in the uxs1 mutant. Taken together, these findings reveal a previously unrecognized regulatory network that connects UDP-GlcUA metabolism to protease-mediated cellular processes and to the transportation of UDP-GlcUA. This newly identified interplay provides a foundation for targeting nucleotide sugar metabolism and protease regulation in the development of improved therapeutic strategies against cryptococcosis.
2025-04-08 | GSE289668 | GEO
Project description:Water soluble carbohydrates (WSC, composed of mainly fructans, sucrose, glucose and fructose) deposited in wheat stems are important carbon sources for grain filling. Variation in stem WSC concentrations among wheat genotypes is one of the genetic factors influencing grain weight and yield under water-limited environments. Here, we describe the molecular dissection of carbohydrate metabolism in stems, at the WSC accumulation phase, of recombinant inbred SB (Seri/Babax) lines of Triticum aestivum differing in stem WSC concentrations. Affymetrix GeneChip analysis of carbohydrate metabolic enzymes revealed that the mRNA levels of two fructan synthetic enzyme families (sucrose:sucrose 1-fructosyltransferase and sucrose:fructan 6-fructosyltransferase) in the stem were positively correlated with stem WSC and fructan concentrations, while the mRNA levels of enzyme families involved in sucrose hydrolysis (sucrose synthase and soluble acid invertase) were inversely correlated with WSC concentrations. Differential regulation of the mRNA levels of these sucrose hydrolytic enzymes in SB lines resulted in genotypic differences in these enzyme activities. Down-regulation of sucrose synthase and soluble acid invertase in high WSC lines was accompanied by significant decreases in the mRNA levels of enzyme families related to sugar catabolic pathways (fructokinase and mitochondrion pyruvate dehydrogenase complex) and enzyme families involved in diverting UDP-glucose to cell wall synthesis (UDP-glucose 6-dehydrogenase, UDP-glucuronate decarboxylase and cellulose synthase), resulting in a reduction in cell wall polysaccharide contents (mainly hemicellulose) in the stem of high WSC lines. These data suggest that differential carbon partitioning in the wheat stem is one mechanism that contributes to genotypic variation in WSC accumulation. We used Affymetrix GeneChip to dissect genotypic variation in carbohydrate metabolism related to water soluble carbohydrate accumulation in stems of wheat. Experiment Overall Design: 8 genotypes of recombinant inbred lines Seri M82 x Babax with 2 biological replicates per genotype. Grown in the field under rain-fed conditions
2008-10-26 | E-GEOD-9767 | biostudies-arrayexpress
Project description:The purpose of this experiment of high-coverage DNA sequencing of 58 frequently mutated genes in hepatocellular carcinoma (HCC) is to confirm clonal distribution of the known HCC drivers in samples corresponding to multiple regions of a tumor.
2020-01-16 | E-MTAB-5899 | biostudies-arrayexpress
Project description:Water soluble carbohydrates (WSC, composed of mainly fructans, sucrose, glucose and fructose) deposited in wheat stems are important carbon sources for grain filling. Variation in stem WSC concentrations among wheat genotypes is one of the genetic factors influencing grain weight and yield under water-limited environments. Here, we describe the molecular dissection of carbohydrate metabolism in stems, at the WSC accumulation phase, of recombinant inbred SB (Seri/Babax) lines of Triticum aestivum differing in stem WSC concentrations. Affymetrix GeneChip analysis of carbohydrate metabolic enzymes revealed that the mRNA levels of two fructan synthetic enzyme families (sucrose:sucrose 1-fructosyltransferase and sucrose:fructan 6-fructosyltransferase) in the stem were positively correlated with stem WSC and fructan concentrations, while the mRNA levels of enzyme families involved in sucrose hydrolysis (sucrose synthase and soluble acid invertase) were inversely correlated with WSC concentrations. Differential regulation of the mRNA levels of these sucrose hydrolytic enzymes in SB lines resulted in genotypic differences in these enzyme activities. Down-regulation of sucrose synthase and soluble acid invertase in high WSC lines was accompanied by significant decreases in the mRNA levels of enzyme families related to sugar catabolic pathways (fructokinase and mitochondrion pyruvate dehydrogenase complex) and enzyme families involved in diverting UDP-glucose to cell wall synthesis (UDP-glucose 6-dehydrogenase, UDP-glucuronate decarboxylase and cellulose synthase), resulting in a reduction in cell wall polysaccharide contents (mainly hemicellulose) in the stem of high WSC lines. These data suggest that differential carbon partitioning in the wheat stem is one mechanism that contributes to genotypic variation in WSC accumulation. We used Affymetrix GeneChip to dissect genotypic variation in carbohydrate metabolism related to water soluble carbohydrate accumulation in stems of wheat. Keywords: Genotypic differences in water soluble carbohydrate metabolism in stem
2008-10-16 | GSE9767 | GEO
Project description:This study evaluates the effect circular RNA (circRNA) has on the development of hepatocellular carcinoma (HCC), which has been an area of limited information in the field. Through microarray analysis, we identified and then characterized the circRNA, circEPS15, which is downregulated in HCC tissue compared to noncancerous tissues. Our analysis shows that overexpressing circEPS15 could reduce tumor cell migration through the inhibition of cell cycle signaling pathways, suggesting this circRNA could be a target for novel HCC therapies. Moreover, we show that circEPS15 encodes a functional protein that could contribute to its antitumor effects. We believe that our study makes a significant contribution to the literature because it both clarifies the molecular mechanisms of circRNA in cell growth and development, as well as provides novel marker or target candidates for improving HCC diagnosis and treatment.
2021-01-15 | GSE164803 | GEO
Project description:Multi-omics approaches were utilized to comprehensively analyze the molecular characteristics of hepatocellular carcinoma (HCC) in South Texas (STX) Hispanics. Exome sequencing revealed high mutation frequencies of AXIN2 and CTNNB1, suggesting a predominant activation of the Wnt/beta-catenin pathway. Cell cycles were positively-, and liver functions were negatively-enriched on gene set enrichment analysis of our transcriptomic and proteomic datasets. Enrichments of gene sets representing specific liver metabolic pathways were found to be associated with the dysregulation of corresponding metabolites. Significant reduction of the majority of lipids seen in serum samples of HCC patients and many fatty acids in HCC tumors corroborate negative adipogenesis and lipid metabolism enrichments. We identified two subtypes of HCC using enrichment scores from paired tumor-nontumor samples of STX-Hispanics or TCGA-LIHC. The subtype with better overall survival revealed pronounced positive enrichments of immune-, angiogenesis-, and negative enrichments of liver function-related hallmark gene sets than the other. The former had higher levels of immune checkpoint and immune exhaustion markers. Together, we report molecular features of HCC, specific and non-specific to Hispanics.
2023-07-11 | MSV000092403 | MassIVE
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2026-01-12 | GSE234454 | GEO
Project description:We found that Quaking5 protein, a RNA splicing protein was downregulated in HCC. Collectively, this study uncovers the mechanisms underlying the regulating role of circZKSCAN1 in HCC cancer stem cells and reveals that the new discovered Qki5-circZKSCAN1-FMRP-CCAR1-Wnt signaling axis is of important therapeutic value in improving the treatment of HCC.
2019-02-02 | GSE110048 | GEO