Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA394826 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5834695.fastq.gz | Fastqsanger.gz | |||
| SRR5834696.fastq.gz | Fastqsanger.gz | |||
| SRR5834697.fastq.gz | Fastqsanger.gz | |||
| SRR5834698.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 4 of 4 |
Similar Datasets
Project description:Background & Aims: Hepatocyte nuclear factor 4A (HNF4A) is a master transcription factor (TF) in hepatocytes that regulates metabolism and differentiation. The mechanism of HNF4A in cancer progression remains unclear due to conflicting results observed in numerous studies. We aimed to address the roles of HNF4A in hepatocellular carcinoma (HCC). Methods: We established the HNF4A overexpression and knocking-down stable cells in HCCLM3 and Huh7, and compared the effects of HNF4A on HCC cells in different glucose supply conditions in vitro and in vivo. Pathway inhibitors treatment and phosphatase activity comparisons were performed for signaling pathway analysis. Gene levels in HCC tissues and the clinical information were collected from TCGA for survival analysis. Multiomics approaches including proteomics, TFRE and ChIP-seq were applied to identify HNF4A target genes. Rescue experiments were performed to verify the functions of the potential target genes. Results: We found HNF4A exhibited tumor-suppressive effects on proliferation and migration of HCC cells in glucose-sufficient conditions but tumor-promotive effects in glucose-insufficient conditions. This diverse functionality of HNF4A was dependent upon the AMPK pathway activity. Similarly, the prognosis predicted by HNF4A was also correlated with AMPKa expression level in HCC patients. The potential HNF4A target genes, including NEDD4 and RPS6KA2, are involved in the diverse functionality of HNF4A in response to AMPK activity status. Conclusions: The glucose supply status could be the potential decisive factor to determine functions of HNF4A on HCC cells. The switch of HNF4A between oncogene and tumor suppressor was determined by AMPK activation status, which was correlated with glucose levels.
2019-08-01 | GSE101553 | GEO
Project description:The IER3 (Immediate Early Response 3) gene exhibits a multifaceted role in cancer biology, acting as both a tumor suppressor and an oncogene depending on the specific cancer type. This duality underscores the complexity of molecular pathways. Despite its significance, there is a dearth of studies dedicated to elucidating the exact mechanisms underlying IER3's involvement in cancer development. Recently, we identified that IER3 functions as an oncogene in cervix, breast, and lung cancer cell lines. In this study, we demonstrate for the first time that IER3 acts as a tumor suppressor in Neuroblastoma.
2025-03-13 | GSE279084 | GEO
Project description:The IER3 (Immediate Early Response 3) gene exhibits a multifaceted role in cancer biology, acting as both a tumor suppressor and an oncogene depending on the specific cancer type. This duality underscores the complexity of molecular pathways. Despite its significance, there is a dearth of studies dedicated to elucidating the exact mechanisms underlying IER3's involvement in cancer development. Recently, we identified that IER3 functions as an oncogene in cervix, breast, and lung cancer cell lines. In this study, we demonstrate for the first time that IER3 acts as a tumor suppressor in Neuroblastoma.
2025-03-13 | GSE279085 | GEO
Project description:The mechanism by which tumor cells resist metabolic stress remains unclear, but many oncogenes are known to regulate this process. Accordingly, metabolic stress is closely associated with tumor metastasis. In this study, gene chip technology showed that RHOF, a member of the Rho GTPase family, is an oncogene that is significantly related to hepatocellular carcinoma (HCC) metastasis; however, it has rarely been reported in tumors. This study was aimed to determine the clinicopathological significance and role of RHOF in HCC progression and investigate the associated mechanisms. The results showed that compared to expression in adjacent non-cancerous tissues, RHOF was frequently upregulated in HCC tumor samples and elevated under conditions of glucose deprivation. RHOF expression was associated with TNM stage, T grade, metastasis status, recurrence, and survival in HCC. RHOF also affected cell morphology and promoted migration, invasion, and epithelial–mesenchymal transition (EMT) of HCC cell lines. Analysis of the underlying mechanism showed that RHOF promoted the Warburg effect by upregulating the expression and function of several glycolytic enzymes in HCC cells. This metabolic shift enhanced HCC cell migration and invasion. Specifically, RHOF exerted tumor-promoting effect by directly interacting with AMP-activated protein kinase (AMPK) and increasing the phosphorylation of AMPK. This subsequently affected RAB3D mRNA stability and led to elevated RAB3D expression, thereby amplifying the Warburg effect and malignant biological behaviors of HCC cells. Therefore, RHOF helps tumor cells resist metabolic stress through modulating the Warburg effect and plays a critical role in promoting HCC cell migration, invasion, and EMT, highlighting its important role in remodeling the metastatic microenvironment and regulating tumor metastasis. RHOF shows potential as a new therapeutic target and prognostic biomarker for HCC. We used microarrays to detail the global programme of gene expression associated with hepatocellular carcinoma metastasis and identified distinct classes of deregulated genes during this process.
2023-09-23 | GSE158408 | GEO
Project description:TFEB and TFE3 are transcriptional regulators of the innate immune response, but the mechanisms regulating their activation upon pathogen infection are poorly elucidated. Using C. elegans and mammalian models, we report that the master metabolic modulator 5'-AMP-activated protein kinase (AMPK) and its negative regulator Folliculin (FLCN) act upstream of TFEB/TFE3 in the innate immune response, independently of the mTORC1 signaling pathway. In nematodes, loss of FLCN or overexpression of AMPK confers pathogen resistance via activation of TFEB/TFE3- dependent antimicrobial genes, while ablation of total AMPK activity abolishes this phenotype. Similarly, in mammalian cells, loss of FLCN or pharmacological activation of AMPK induces TFEB/TFE3-dependent pro-inflammatory cytokine expression. Importantly, a rapid reduction in cellular ATP levels in murine macrophages is observed upon lipopolysaccharide (LPS) treatment accompanied by an acute AMPK activation and TFEB nuclear localization. These results uncover an ancient, highly conserved and pharmacologically actionable mechanism coupling energy status with innate immunity.
2019-03-08 | GSE128030 | GEO
Project description:TFEB and TFE3 are transcriptional regulators of the innate immune response, but the mechanisms regulating their activation upon pathogen infection are poorly elucidated. Using C. elegans and mammalian models, we report that the master metabolic modulator 5'-AMP-activated protein kinase (AMPK) and its negative regulator Folliculin (FLCN) act upstream of TFEB/TFE3 in the innate immune response, independently of the mTORC1 signaling pathway. In nematodes, loss of FLCN or overexpression of AMPK confers pathogen resistance via activation of TFEB/TFE3- dependent antimicrobial genes, while ablation of total AMPK activity abolishes this phenotype. Similarly, in mammalian cells, loss of FLCN or pharmacological activation of AMPK induces TFEB/TFE3-dependent pro-inflammatory cytokine expression. Importantly, a rapid reduction in cellular ATP levels in murine macrophages is observed upon lipopolysaccharide (LPS) treatment accompanied by an acute AMPK activation and TFEB nuclear localization. These results uncover an ancient, highly conserved and pharmacologically actionable mechanism coupling energy status with innate immunity.
2019-03-08 | GSE128029 | GEO
Project description:Proteasomes undergo dynamic nucleocytoplasmic translocation and phase transitions in response to glucose starvation. AMP-activated protein kinase (AMPK) is important for cytoplasmic proteasome condensate dissolution and proteasome nuclear reentry in budding yeast cells upon glucose refeeding of quiescent cells. This study demonstrates that AMPK interacts with proteasomes, and the AMPK pathway regulates proteasome phosphorylation status and condensate solubility during reversible proteasome condensate formation. AMPK and the PP1 phosphatase dynamically regulate phosphorylation of multiple proteasome subunits. Therefore, the regulation of proteasome phosphorylation by AMPK is likely to be central to proteasome biomolecular condensate formation and dissolution.
| PXD065670 |
Project description:The serine/threonine kinase LKB1 is a tumor suppressor gene which also plays key roles in metabolic function in peripheral tissues through its direct phosphorylation and activation of the AMP-activated protein kinase (AMPK). The LKB1/AMPK pathway plays key roles in the liver in suppressing transcriptional programs of gluconeogenesis and lipogenesis, and hepatic LKB1 is required for the ability of the type 2 diabetes agent metformin to lower blood glucose levels in mice. To more broadly define how the LKB1/AMPK pathway controls hepatic metabolism, transcriptional profiling was employed using mice with an inducible liver-specific deletion of Lkb1. Unexpectedly, LKB1/AMPK signaling broadly controls the expression of many phase I xenobiotic metabolism genes, including several members of the cytochrome P450 family. In particular, expression of CYP2E1, an important mediator of drug detoxification, was markedly reduced upon LKB1 loss. LKB1 liver-specific knockout mice exposed to hepatocarcinogens, exhibited marked resistance to carcinogen-induced hepatocyte apoptosis, proliferation, senescence, and liver fibrosis and tumorigenesis.
2019-05-01 | GSE21984 | GEO
Project description:Activation transcription factor 2 (ATF2), a member of the ATF/CREB family of transcription factors, is implicated in a broad spectrum of cancer-related biological functions, such as cell proliferation, apoptosis and DNA repair. Growing evidence indicates ATF2 act as an oncogene or a tumor suppressor in different cancer types depending on its expression level and subcellular localization. In this study, RNA-seq and ChIP-seq were performed for identification of genome-wide DNA binding sites and potential transcription targets for ATF2.
2024-09-01 | GSE212685 | GEO
Project description:Activation transcription factor 2 (ATF2), a member of the ATF/CREB family of transcription factors, is implicated in a broad spectrum of cancer-related biological functions, such as cell proliferation, apoptosis and DNA repair. Growing evidence indicates ATF2 act as an oncogene or a tumor suppressor in different cancer types depending on its expression level and subcellular localization. In this study, RNA-seq and ChIP-seq were performed for identification of genome-wide DNA binding sites and potential transcription targets for ATF2.
2024-09-01 | GSE212684 | GEO