Targeting lipid metabolism in pancreatic cancer [CRISPR]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1074767 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Targeting lipid metabolism in pancreatic cancer
| PRJNA1074769 | ENA
Project description:Pancreatic ductal adenocarcinoma (PDAC) thrives in a nutrient-deprived microenvironment, making it particularly susceptible to treatments that interfere with cancer metabolism. For example, PDAC utilizes and is dependent on high levels of autophagy and other lysosomal processes. Although targeting these pathways has shown potential in pre-clinical studies, progress has been hampered by the challenge of identifying and characterizing favorable targets for drug development. Here, we characterize PIKfyve, a lipid kinase integral to lysosomal functioning as a novel and targetable vulnerability in PDAC. Through comprehensive metabolic analyses we find that PIKfyve inhibition obligates PDAC to upregulate de novo lipid synthesis, a relationship previously undescribed. PIKfyve inhibition triggers a distinct lipogenic gene expression and metabolic program, creating a dependency on de novo lipid metabolism pathways, including genes such as FASN and ACACA. These results suggest that targeting PIKfyve disrupts lysosome-dependent lipid metabolism in PDAC and may be a favorable metabolic target for therapeutic development. Further, this data suggests that one could take advantage of this synthetic dependency by co-targeting PIKfyve and FASN or ACACA as a therapeutic strategy.
2024-04-10 | GSE255375 | GEO
Project description:Targeting lipid metabolism in pancreatic cancer [RNA-seq]
| PRJNA1074765 | ENA
Project description:Pancreatic ductal adenocarcinoma (PDAC) thrives in a nutrient-deprived microenvironment, making it particularly susceptible to treatments that interfere with cancer metabolism. For example, PDAC utilizes and is dependent on high levels of autophagy and other lysosomal processes. Although targeting these pathways has shown potential in pre-clinical studies, progress has been hampered by the challenge of identifying and characterizing favorable targets for drug development. Here, we characterize PIKfyve, a lipid kinase integral to lysosomal functioning as a novel and targetable vulnerability in PDAC. Through comprehensive metabolic analyses we find that PIKfyve inhibition obligates PDAC to upregulate de novo lipid synthesis, a relationship previously undescribed. PIKfyve inhibition triggers a distinct lipogenic gene expression and metabolic program, creating a dependency on de novo lipid metabolism pathways, including genes such as FASN and ACACA. These results suggest that targeting PIKfyve disrupts lysosome-dependent lipid metabolism in PDAC and may be a favorable metabolic target for therapeutic development. Further, this data suggests that one could take advantage of this synthetic dependency by co-targeting PIKfyve and FASN or ACACA as a therapeutic strategy.
2024-04-10 | GSE255377 | GEO
Project description:Pathways that stimulate β-cell regeneration remain of great clinical interest, yet effective therapeutic avenues that promote survival or reconstitution of β-cell mass remain elusive. Utilizing a mouse model with inducible β-cell apoptosis followed by adiponectin-mediated regeneration, we aimed to identify key molecules boosting β-cell viability. Within the regenerating pancreatic islets, we examined changes within the transcriptome, and observed an extensive upregulation of genes encoding proteins involved in lipid transport and metabolism. The most prominent targets were further confirmed by quantitative PCR and immunofluorescence. Among the upstream regulators predicted by pathway analysis of the transcriptome, we detected enhanced levels of two key transcription factors, HNF4α and PPARα. Enhanced leptin levels in circulation may also contribute to the anti-lipotoxic program in islets. In summary, our data suggest that improving local lipid metabolism as an important anti-lipotoxic phenomenon to boost β-cell regeneration, primarily mediated by adiponectin’s action on the β-cells directly as well as on the adipocyte. RNA profiles of pancreatic islets isolated from PANIC-ATTAT mice crossed with adiponectin wild-type (P-Adn+/+) or the overexpressing transgene (P-AdnTg/+) at 5 weeks after initial dimerizer administration.
2015-01-09 | E-GEOD-64787 | biostudies-arrayexpress
Project description:Pathways that stimulate β-cell regeneration remain of great clinical interest, yet effective therapeutic avenues that promote survival or reconstitution of β-cell mass remain elusive. Utilizing a mouse model with inducible β-cell apoptosis followed by adiponectin-mediated regeneration, we aimed to identify key molecules boosting β-cell viability. Within the regenerating pancreatic islets, we examined changes within the transcriptome, and observed an extensive upregulation of genes encoding proteins involved in lipid transport and metabolism. The most prominent targets were further confirmed by quantitative PCR and immunofluorescence. Among the upstream regulators predicted by pathway analysis of the transcriptome, we detected enhanced levels of two key transcription factors, HNF4α and PPARα. Enhanced leptin levels in circulation may also contribute to the anti-lipotoxic program in islets. In summary, our data suggest that improving local lipid metabolism as an important anti-lipotoxic phenomenon to boost β-cell regeneration, primarily mediated by adiponectin’s action on the β-cells directly as well as on the adipocyte.
2015-01-09 | GSE64787 | GEO
Project description:Mutant GNAS drives pancreatic tumorigenesis by inducing PKA-mediated SIK suppression and reprogramming lipid metabolism
| PRJNA471090 | ENA
Project description:Lipid metabolism genes in first trimester placenta
| PRJNA848825 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-04-10 | GSE255378 | GEO
Project description:Gene expression profiling was carried out in Huh-7.5 cells in which miR-27a was over- or under-expressed. Transfection of cells with pre-miR-27a and pre-miR-control, or anti-miR-27a and anti-miR-control enabled down- and up-regulated genes to be determined, respectively. Replication and infectivity of the lipotrophic hepatitis C virus (HCV) is regulated by cellular lipid status. Among differentially expressed micro (mi)RNAs, we found that miR-27a was preferentially expressed in HCV-infected compared with hepatitis B virus (HBV)-infected liver. Gene expression profiling of Huh-7.5 cells showed that miR-27a regulates lipid metabolism by targeting the lipid synthetic transcriptional factor, RXRα, and the lipid transporter, ABCA1 Carrying out a Target Scan (Release 5.2) of miR-27a predicted 921 candidate target genes, and functional gene ontology enrichment analysis of these genes by MetaCore (Thomson Reuters, NY) showed that miR-27a could target the signaling pathways of cytoskeleton remodeling and lipid metabolism . To examine whether these signaling pathways were regulated by miR-27a, gene expression profiling was carried out in Huh-7.5 cells in which miR-27a was over- or under-expressed. Transfection of cells with pre-miR-27a and pre-miR-control, or anti-miR-27a and anti-miR-control enabled down- and up-regulated genes to be determined, respectively. Huh-7.5 cells with miR-27a over- or under-expressed
2013-06-05 | E-GEOD-41737 | biostudies-arrayexpress