Study of transcriptional effects of FOXS1 silencing and TGF-beta treatment in SNU-449 hepatocellular carcinoma cell line
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA625739 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Background & aims: Transforming Growth Factor beta (TGFβ) is a pleiotropic cytokine which controls fundamental cellular processes associated with tumor onset and progression. In hepatocellular carcinoma (HCC), we previously highlighted TGFβ signatures recapitulating its functional duality (i.e. cytostatic versus pro-metastatic features) to discriminate patients with good and poor prognosis. Here, we aimed at characterizing Forkhead Box S1 (FOXS1), a predicted transcription factor that we hypothesize to mediate pro-metastatic properties of TGFβ. Methods: FOXS1 expression was profiled in well-characterized HCC cell lines. Transient loss of function of FOXS1 (siRNA) was combined with functional assays and analysis of epithelial-mesenchymal transition (EMT) markers by western blot and immunofluorescence. Clinical relevance of FOXS1 was determined by integrative genomics. Results: Our data show that FOXS1 is a novel canonical SMAD-dependent TGFβ target. Its expression correlates with a mesenchymal phenotype. FOXS1 mediates pro-metastatic properties of TGFβ by inducing EMT and cell migration. In human HCC, FOXS1 correlates with VIM expression and is highly expressed in specific molecular subtypes associated with a poorer differentiation and no CTNNB1 mutation. FOXS1 expression predicts a poor prognosis (e.g. reduced patient survival) in liver, colon, stomach and kidney cancer. Conclusions: FOXS1 is a novel TGFβ target and a key mediator of EMT. Its induction in cancer is associated with a poor prognosis. Thus, determining the expression of FOXS1 in advanced tumors in which the pro-metastatic arm of TGFβ is activated could help to identify patients who may benefit from targeted therapies using TGFβ inhibitors.
2022-06-15 | GSE148795 | GEO
Project description:Transforming Growth Factor beta (TGF-beta) is a pleiotropic cytokine playing a key role in liver carcinogenesis. The goal of this study was to identify genes differentially expressed in hepatocellular carcinoma cell lines PRC/PRF/5 and SNU-449 after a treatment with TGF-beta and/or Galunisertib, an inhibitor of the type I TGF-beta receptor (TGFBRI). Thus, cells were treated for 16 hours with 1 ng/mL recombinant human TGF-β1 (R&D Systems, Minneapolis, MN) and/or 10 μM LY2157299 (Sigma-Aldrich, St. Louis, MO) after overnight serum starvation. Gene expression profiling was performed using Agilent SurePrint G3 Human GE 8x60K microarrays.
2023-06-01 | GSE211806 | GEO
Project description:Expression data from SNU-449 cells transfected with USP48
| PRJNA1101422 | ENA
Project description:RNA-seq of Snu-449 cells treated with Ezetimibe or control
| PRJNA938039 | ENA
Project description:Human SNU cell lines derived from hepatocellular carcinomas associated with chronic hepatitis B virus (HBV) infection were examined. The analysis of intracellular RNA and DNA markers of HBV replication and examination of HBV RNA reads coverage of selected regions on HBV-related RNAs and polyadenylation positions within HBV sequence using RNA-sequencing suggested absence of HBV replication in SNU-423, SNU-368 SNU-398, SNU-182, SNU-449, SNU-475, SNU-354, SNU-739 and SNU-387 cells, while SNU-761 and SNU-886 still could maintain residual HBV replication. The undetectable intracellular HBV core antigen (HBcAg) and absence of significant levels of secreted core-associated and virion-associated HBV DNA confirmed the absence or profound suppression of HBV replication in parental SNU cell lines. Various 5'-human-HBV-3' and 5'-HBV-human-3' RNAs transcribed from integrated HBV DNA were found in most of SNU cell lines. The 5'-HBV-human-3' junctions suggested that several SNU cell lines could generate 5'-HBV-human-3' RNAs encoding HBV envelope proteins. The known and novel spliced HBV RNAs were detected in SNU-886, SNU-739, SNU-387, SNU-761, and SNU-354 cells. At least some of them were generated independently of HBV replication. All SNU cell lines could not support efficient HBV replication after transfection with the vector initiating efficient HBV replication in Huh7 cells. This was reflected by three distinct accumulation patterns of HBV replication markers, undetectable intracellular HBcAg, and by the lack of considerable levels of secreted core-bound and virion-associated HBV DNA. Overall, SNU cell lines represent valuable model systems for detailed analysis of integrant-transcribed HBV RNAs, spliced HBV RNAs, and mechanisms of suppression of HBV genome replication.
2025-09-15 | GSE298154 | GEO
Project description:RNA transcriptome sequencing analysis was performed in SNU-668 Erastin-resistant cells and SNU-668 parental cells, SNU-484 RSL3-resistant cells and SNU-484 parental cells
2024-04-04 | GSE262114 | GEO
Project description:White adipose tissue (WAT) fibrosis is a major determinant of obesity-induced cardiometabolic dysfunction and is characterized by excessive extracellular matrix (ECM) deposition and myofibroblast activation. Transforming growth factor (TGF)-β1 is a profibrotic cytokine that potently induces myofibroblast activation in adipocyte stem cells (ASC). How TGF-β1 orchestrates ASC activation in WAT fibrosis is not completely understood. We identified FOXS1, a member of the forkhead box transcription factor superfamily, as a transcriptional target of TGF-β1 signaling in primary human WAT ASC (hASC). FOXS1 potentiated TGF-β1-dependent upregulation of several myofibroblast genes (e.g. Acta2, Col1a1, Fn1, Il11) in 10T1/2 fibroblasts. FOXS1 also mitigated the induction of several adipogenic factors (e.g. Pparg, Stat5a, Fabp4, Adipoq) in 10T1/2 fibroblasts and sensitized these cells to the anti-adipogenic effects of TGF-β1. Furthermore, loss of endogenous FOXS1 improved adipogenic permissiveness and activated proadipogenic gene programs in 10T1/2 cells, even after TGF-β1 stimulation. These results indicate that FOXS1 is a positive regulator of profibrotic TGF-β1-dependent cellular responses, orchestrating the regulation of molecular phenotypes that promote myofibroblast activation and block adipogenesis. These findings offer novel insight into the TGF-β1-dependent roles of FOXS1 in fibroblasts within the context of profibrotic ASC activation and provide a foundation for further investigation into the role of FOXS1 in WAT fibrosis and obesity-induced cardiometabolic dysfunction.
2025-08-01 | GSE302340 | GEO
Project description:White adipose tissue (WAT) fibrosis is a major determinant of obesity-induced cardiometabolic dysfunction and is characterized by excessive extracellular matrix (ECM) deposition and myofibroblast activation. Transforming growth factor (TGF)-β1 is a profibrotic cytokine that potently induces myofibroblast activation in adipocyte stem cells (ASC). How TGF-β1 orchestrates ASC activation in WAT fibrosis is not completely understood. We identified FOXS1, a member of the forkhead box transcription factor superfamily, as a transcriptional target of TGF-β1 signaling in primary human WAT ASC (hASC). FOXS1 potentiated TGF-β1-dependent upregulation of several myofibroblast genes (e.g. Acta2, Col1a1, Fn1, Il11) in 10T1/2 fibroblasts. FOXS1 also mitigated the induction of several adipogenic factors (e.g. Pparg, Stat5a, Fabp4, Adipoq) in 10T1/2 fibroblasts and sensitized these cells to the anti-adipogenic effects of TGF-β1. Furthermore, loss of endogenous FOXS1 improved adipogenic permissiveness and activated proadipogenic gene programs in 10T1/2 cells, even after TGF-β1 stimulation. These results indicate that FOXS1 is a positive regulator of profibrotic TGF-β1-dependent cellular responses, orchestrating the regulation of molecular phenotypes that promote myofibroblast activation and block adipogenesis. These findings offer novel insight into the TGF-β1-dependent roles of FOXS1 in fibroblasts within the context of profibrotic ASC activation and provide a foundation for further investigation into the role of FOXS1 in WAT fibrosis and obesity-induced cardiometabolic dysfunction.
2025-08-01 | GSE302341 | GEO
Project description:Transcriptional profiling of human hepatocarcinoma comparing Huh-7 and SNU-739. Two-condition experiment, normalized ratio represented by Huh-7/SNU-739. Biological replicates: 2 Huh-7 replicates, 2 SNU-739 replicates.
2014-04-29 | E-GEOD-57106 | biostudies-arrayexpress
Project description:a microarray analysis of long noncoding RNAs was performed in exosomes from SNU-668 Erastin-resistant cells and parental SNU-668 cells
2022-09-02 | GSE212303 | GEO