USF1 transcriptionally regulated UGT1A3 and promoted lung adenocarcinoma progression by regulating neurotrophin signaling pathway
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PROVIDER: PRJNA783871 | ENA |
REPOSITORIES: ENA
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Project description:Lung cancer remains the leading cause of oncological death. There is an urgent need to discover new molecular targets and to develop new treatments. Our previous study showed that one of the UDP-glucuronosyltransferases (UGTs) family, UGT1A3, is an important prognostic factor for lung adenocarcinoma (LUAD), inhibiting UGT1A3 could significantly improve the efficacy of anti-tumor drugs. In this study, we aimed to explore the upstream transcriptional factor (USF1) of UGT1A3 and its way of playing a role in LUAD.
2023-11-13 | GSE189607 | GEO
Project description:Liver cancer, including hepatocellular carcinoma (HCC), is a malignant tumor type with high metastasis and mortality rate in worldwide. Upstream transcription factor 1 (USF1) is a canonical transcription factor (TF) and associated with the pathogenesis of several cancers, while its biological functions and molecular targets in HCC are not clear. In this study, we overexpressed USF1 in Huh7 cells and used whole transcriptome profile sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) methods to systematically investigate the downstream targets of USF1. Following polymerase chain reaction (PCR) was used to validate the downstream targets. Based on the results, we found USF1 significantly regulated 350 differentially expressed genes (DEGs). Up DEGs were mainly protein coding genes, and enriched in immune and inflammation response pathways; while down DEGs were mainly lncRNAs, indicating the regulatory feature of USF1. We also detected USF1 directly bound to the promoter region of 2492 genes, which may deeply participate in the viral progression and cell proliferation pathways. By integrating these two datasets, we detected 16 overlapped genes, including down lncRNA-NEAT1 and up TF-ETV5. Down lncRNA-NEAT1 showed reverse expression pattern and prognosis result to USF1 in liver cancer patients, while up TF-ETV5 showed consistent result to USF1. Promoter region motif analysis indicated that ETV5 had more binding motifs and genes than USF1 itself for USF1-regulated DEGs, indicating that USF1 may indirectly modulate gene expression by regulating ETV5 expression in Huh7 cells. Finally, we validated the direct interaction between USF1 and the promoter of ETV5 using ChIP-qPCR. In summary, our results demonstrated that USF1 binds to the promoter region of thousands of genes, and affects large part of DEGs by indirectly manner. The downstream genes, including lncRNA-NEAT1 and TF-ETV5, may also tightly participate in the regulated network by USF1 and have potential functions in the progression of HCC. The USF1 and its downstream targets could be used as potential targets for HCC therapy in future.
2023-09-28 | GSE232262 | GEO
Project description:Liver cancer, including hepatocellular carcinoma (HCC), is a malignant tumor type with high metastasis and mortality rate in worldwide. Upstream transcription factor 1 (USF1) is a canonical transcription factor (TF) and associated with the pathogenesis of several cancers, while its biological functions and molecular targets in HCC are not clear. In this study, we overexpressed USF1 in Huh7 cells and used whole transcriptome profile sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) methods to systematically investigate the downstream targets of USF1. Following polymerase chain reaction (PCR) was used to validate the downstream targets. Based on the results, we found USF1 significantly regulated 350 differentially expressed genes (DEGs). Up DEGs were mainly protein coding genes, and enriched in immune and inflammation response pathways; while down DEGs were mainly lncRNAs, indicating the regulatory feature of USF1. We also detected USF1 directly bound to the promoter region of 2492 genes, which may deeply participate in the viral progression and cell proliferation pathways. By integrating these two datasets, we detected 16 overlapped genes, including down lncRNA-NEAT1 and up TF-ETV5. Down lncRNA-NEAT1 showed reverse expression pattern and prognosis result to USF1 in liver cancer patients, while up TF-ETV5 showed consistent result to USF1. Promoter region motif analysis indicated that ETV5 had more binding motifs and genes than USF1 itself for USF1-regulated DEGs, indicating that USF1 may indirectly modulate gene expression by regulating ETV5 expression in Huh7 cells. Finally, we validated the direct interaction between USF1 and the promoter of ETV5 using ChIP-qPCR. In summary, our results demonstrated that USF1 binds to the promoter region of thousands of genes, and affects large part of DEGs by indirectly manner. The downstream genes, including lncRNA-NEAT1 and TF-ETV5, may also tightly participate in the regulated network by USF1 and have potential functions in the progression of HCC. The USF1 and its downstream targets could be used as potential targets for HCC therapy in future.
2023-09-28 | GSE232261 | GEO
Project description:Overexpression of USF1 in HEK293T cells in vitro to ascertain the genes downstream of USF1. Will identify direct targets as well as indirect targets of USF1. Keywords: Overexpression of transcription factor to determine downstream targets.
2009-09-14 | GSE17300 | GEO
Project description:Overexpression of USF1 in HEK293T cells in vitro to ascertain the genes downstream of USF1. Will identify direct targets as well as indirect targets of USF1. Keywords: Overexpression of transcription factor to determine downstream targets. Cloned USF1 from cDNA and transiently transfected into HEK293T cells. Total RNA collected 48 hours after transfection. Empty vector used as control. Expression of USF1 was validated using western blot, and qRT-PCR was used to validate differential expression.
2009-09-14 | E-GEOD-17300 | biostudies-arrayexpress
Project description:Comparison of gene expression for individuals affected with FCHL exhibiting the USF1 susceptibility haplotype and FCHL affected indiviuals carrying the protective haplotype Keywords: ordered
2004-02-29 | GSE590 | GEO
Project description:Analysis of adenovirus-mediated USF1 overexpression in liver at gene expression level. Results provide important information of the response of mouse liver to USF1 overexpression, such as specific USF1-induced, suppressed, up- or down-regulated genes invovled in metabolism and immune responses.
2010-03-31 | GSE17442 | GEO
Project description:Analysis of adenovirus-mediated USF1 overexpression in liver at gene expression level. Results provide important information of the response of mouse liver to USF1 overexpression, such as specific USF1-induced, suppressed, up- or down-regulated genes invovled in metabolism and immune responses. Total RNA isolated from whole mouse liver 5 days post tail vein injection of adenovirus carrying either hUSF1 cDNA or eGFP alone as control vector.
2010-04-13 | E-GEOD-17442 | biostudies-arrayexpress
Project description:Macrophage function declines with age, however the underlying mechanisms remain poorly understood. Here, we report that MYC and USF1 are key in driving age-related macrophage functional decline in humans, including reduction in phagocytosis and chemotaxis. We show downregulation with age of MYC and USF1 in human monocyte-derived macrophages (MDMs) and crucially, that knockdown of MYC or USF1 in young MDMs modelled the age-related functional changes. Transcriptomic analysis of these young knockdown MDMs revealed alteration in expression of genes crucial to these functions, as well as those linked to adhesion and extracellular matrix formation. Concordant dysregulation of these genes was also seen in older MDMs. Finally, we show that morphology and F-actin content were altered with loss of MYC or USF1, similarly to that seen in ageing. Together, these results define MYC and USF1 as key drivers of MDM age-related functional decline and identify downstream targets to improve macrophage function in ageing.
2024-04-10 | GSE240075 | GEO
Project description:Epidemiological studies indicate a bidirectional association between metabolic disturbances, including obesity and related pathological states, and mood disorders, most prominently major depression. However, the biological mechanisms mediating the comorbid relationship between the deranged metabolic and mood states remain incompletely understood. Here we tested the hypothesis that the enhanced activation of brown fat tissue (BAT), known to beneficially regulate obesity and accompanying dysfunctional metabolic states is also paralleled by an alteration of affective behaviour. We used upstream stimulatory factor 1 (USF1) knock-out mice as a genetic model of constitutively activated BAT with a positive cardiometabolic profile and find a reduction of depression- and anxiety-like behaviour associated with USF1 deficiency. Surgical removal of interscapular BAT did not impact the behavioural phenotype of USF1 KO mice which was not accompanied by alterations of neural progenitor cell proliferation, differentiation or survival in the hippocampal dentate gyrus. RNAseq analysis characterized the molecular signature of USF1 deficiency in the hippocampus and revealed a significant increase in the expression of several members of the X-linked lymphocyte-regulated (xlr) genes, including xlr3b and xlr4b, implicated in the regulation of dendritic branching, dendritic spine number and morphology. These molecular changes were accompanied by morphological alterations in hippocampal neurons, manifested reduced dendritic length and complexity. Collectively these data suggest that the metabolic regulator USF1 is involved in the control of affective behaviour in mice and that this modulation of mood states is unrelated to USF1-dependent BAT activation, but instead associates with structural changes in the brain.
2022-05-27 | GSE204675 | GEO