Effect of overepression of HK1 in hepatocellular carcinoma cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE297965 | GEO | 2026/03/18
REPOSITORIES: GEO
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Project description:Purpose: The goals of this study are to compare the gene expression profile of Huh7 cells treated with different ectosomes or not and to evaluate the function of ectosomal Hexokianse 1 (HK1) derived from HSCs. Methods: Firstly, we treated different LX-2 HSCs with TGF-β (2 ng/mL) for 36 hours to activate HSCs, then ectosomes from LX-2 or HK1-KD LX-2 culture medium were isolated respectively by differential centrifugation processes. Secendly, Huh7 cells were preincubated with different ectosomes or not for 12 hours and then fresh medium for another 12 hours. Lastly, different groups of Huh7 cells were prepared for RNA-seq. Results: By Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the differentially expressed genes, a total of 124 pathways were found to be enriched in the ectosome-incubated Huh7 cells compared with the control Huh7 cells, while a total of 36 pathways were enriched in the ectosome-incubated Huh7 cells compared with the HK1-KD ectosome-incubated Huh7 cells.Gene set enrichment analysis (GSEA) also revealed enrichment of the N-glycosylation pathway in the ectosome-incubated Huh7 cells compared with the control Huh7 cells. Conversely, this pathway was negatively regulated in Huh7 cells incubated with HK1-KD HSC-derived ectosomes Conclusion: the transferal of HSC-derived ectosomal HK1 into HCC cells regulates the N-glycosylation level of Huh7.
2024-04-28 | GSE173632 | GEO
Project description:In response to a myriad of stimuli quiescent resident cardiac fibroblasts undergo metabolic, morphological, and functional alterations to transition to myofibroblasts and mediate cardiac fibrosis. In the present study we investigated the contribution of interferon regulatory factor 7 (IRF7) to fibroblast activation and cardiac fibrosis. IRF7 knockdown in quiescent cardiac fibroblasts potentiated whereas IRF7 over-expression suppressed myofibroblast transition. Consistently, targeted deletion of IRF7 fibroblasts/myofibroblasts similarly exacerbated cardiac fibrosis and dampened heart function in animal models of heart failure. Integrated transcriptomic analysis uncovered Hexokinase 1 (Hk1) as a downstream target for IRF7. Congruently, genetic deletion or pharmaceutical inhibition of HK1 protected the mice from adverse cardiac remodeling. Mechanistically, HK1 contributed to cellular lactate pool to promote histone H3K9 lactylation thus licensing the transcription of pro-fibrogenic molecules. Finally, the relevance of the IRF7-HK1 axis was authenticated in human heart specimens. In conclusion, our data unveil a previously unrecognized IRF7-HK1 axis that contributes to metaboloepigenetic reprogramming of fibroblast activation and cardiac fibrosis. Targeting this axis might yield novel therapeutic solutions for the intervention of heart failure.
2026-04-09 | GSE317712 | GEO
Project description:In response to a myriad of stimuli quiescent resident cardiac fibroblasts undergo metabolic, morphological, and functional alterations to transition to myofibroblasts and mediate cardiac fibrosis. In the present study we investigated the contribution of interferon regulatory factor 7 (IRF7) to fibroblast activation and cardiac fibrosis. IRF7 knockdown in quiescent cardiac fibroblasts potentiated whereas IRF7 over-expression suppressed myofibroblast transition. Consistently, targeted deletion of IRF7 fibroblasts/myofibroblasts similarly exacerbated cardiac fibrosis and dampened heart function in animal models of heart failure. Integrated transcriptomic analysis uncovered Hexokinase 1 (Hk1) as a downstream target for IRF7. Congruently, genetic deletion or pharmaceutical inhibition of HK1 protected the mice from adverse cardiac remodeling. Mechanistically, HK1 contributed to cellular lactate pool to promote histone H3K9 lactylation thus licensing the transcription of pro-fibrogenic molecules. Finally, the relevance of the IRF7-HK1 axis was authenticated in human heart specimens. In conclusion, our data unveil a previously unrecognized IRF7-HK1 axis that contributes to metaboloepigenetic reprogramming of fibroblast activation and cardiac fibrosis. Targeting this axis might yield novel therapeutic solutions for the intervention of heart failure.
2026-04-09 | GSE317630 | GEO
Project description:Extracellular vesicles play crucial roles in intercellular communication in tumor microenvironment. Here, we demonstrate that in hepatic fibrosis, TGF-β stimulates the palmitoylation of hexokinase 1 (HK1) in hepatic stellate cells (HSCs), which facilitates the secretion of HK1 via large extracellular vesicles (lEVs) in a TSG101-dependent manner. The lEV HK1 is hijacked by hepatocellular carcinoma (HCC) cells, leading to accelerated glycolysis and HCC progression. In HSCs, the nuclear receptor Nur77 transcriptionally activates the expression of depalmitoylase ABHD17B to inhibit HK1 palmitoylation, consequently attenuating HK1 release. However, TGF-β-activated Akt functionally represses Nur77 by inducing Nur77 phosphorylation and degradation. We identify a small molecule PDNPA that binds Nur77 to generate steric hindrance to block Akt targeting, thereby disrupting Akt-mediated Nur77 degradation and preserving Nur77 inhibition of HK1 release. Together, this study demonstrates an overlooked function of HK1 in HCC upon its release from HSCs and highlights PDNPA as a candidate compound for inhibiting HCC progression.
2022-08-09 | PXD035911 |
Project description:A primary role of the liver is to regulate whole body glucose homeostasis. Glucokinase (GCK) is the main hexokinase (HK) expressed in hepatocytes and functions to phosphorylate the glucose that enters via GLUT transporters to become glucose-6-phosphate (G6P), which subsequently commits glucose to enter downstream anabolic and catabolic pathways. In the recent years, Hexokinase Domain-Containing-1 (HKDC1), a novel 5th HK, has been characterized by our group and others. Its expression profile varies but has been identified to have low basal expression in normal liver but increases during states of stress including pregnancy, nonalcoholic fatty liver disease (NAFLD), and liver cancer. Here, we have developed a stable overexpression model of hepatic HKDC1 in mice to examine its effect on metabolic regulation. We found that HKDC1 overexpression, over time, causes impaired glucose homeostasis in male mice and shifts glucose metabolism towards anabolic pathways with an increase in nucleotide synthesis. Furthermore, we observed these mice to have larger liver sizes due to greater hepatocyte proliferative potential and cell size, which in part, is mediated via Yes-associated protein (YAP) signaling
2023-03-20 | GSE227535 | GEO
Project description:Differential gene expression in RNA isolated from stably-transfected EBERs-negative versus EBERs-positive HK1 cell lines We established stable transfection of EBERs in the EBV-negative NPC cell line, HK1,to elucidate the role of the EBERs in NPC pathogenesis. Microarray gene expression profiling was carried out to investigate candidate genes which expression correlates with the expression of the EBERs. Total RNA was extracted from each cell line and processed using GeneChip® Whole Transcript (WT) Sense Target Labelling Assay and then analyzed with GeneChip® Human Gene 1.0 ST Array, with three repeats. Candidate genes differentially expressed between the two transfected HK1 cell lines were identified using GeneSpring GX 10 (Agilent Technologies).
2012-12-31 | E-GEOD-29123 | biostudies-arrayexpress
Project description:Differential gene expression in RNA isolated from stably-transfected EBERs-negative versus EBERs-positive HK1 cell lines We established stable transfection of EBERs in the EBV-negative NPC cell line, HK1,to elucidate the role of the EBERs in NPC pathogenesis. Microarray gene expression profiling was carried out to investigate candidate genes which expression correlates with the expression of the EBERs.
2012-12-31 | GSE29123 | GEO
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