Cancer-cell-secreted miR-9-5p regulates cholesterol homeostasis to promote tumor metastasis [vehicle and 25-HC]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA922896 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23048561_1.fastq.gz | Fastqsanger.gz | |||
| SRR23048561_2.fastq.gz | Fastqsanger.gz | |||
| SRR23048562_1.fastq.gz | Fastqsanger.gz | |||
| SRR23048562_2.fastq.gz | Fastqsanger.gz | |||
| SRR23048563_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 12 |
Similar Datasets
Project description:To investigate the effects of 25-HC on the polarization of macrophage RAW264.7,RAW264.7 cells treated with 25-HC and untreated control were collected for RNA sequencing We then performed gene expression profiling analysis using data obtained from RNA-seq of RAW264.7 cell treated with 25-HC and untreated control
2024-08-31 | GSE222623 | GEO
Project description:Cancer-cell-secreted miR-9-5p regulates cholesterol homeostasis to promote tumor metastasis
| PRJNA923237 | ENA
Project description:Background: Non-alcoholic fatty liver disease (NAFLD) is a complex multifactorial disorder that is characterised by dysfunctional lipid metabolism and cholesterol homeostasis, and a related chronic inflammatory response. NAFLD has become the most common cause of chronic liver disease in many countries, and its prevalence continues to rise in parallel with increasing rates of obesity. Here, we evaluated the putative NAFLD-attenuating effects of a multicomponent medicine consisting of 24 ingredients: Hepar compositum (HC-24). Methods: Ldlr-/-.Leiden mice were fed a high-fat diet (HFD) with a macronutrient composition and cholesterol content comparable to human diets for 24 weeks to induce obesity-associated metabolic dysfunction, including hepatic steatosis and inflammation. HC-24 or vehicle control was administered intraperitoneally 3 times/week (1.5 ml/kg) for the last 18 weeks of the study. Histological analyses of liver and adipose tissue were combined with extensive hepatic transcriptomics analysis (next generation sequencing). Transcriptomics results were further substantiated with immunohistochemical and liver lipid analyses. Results: HFD feeding induced obesity and metabolic dysfunction that was associated with adipose tissue inflammation and increased gut permeability. In the liver, HFD-feeding resulted in a disturbance of cholesterol homeostasis and an associated inflammatory response. HC-24 did not affect body weight, metabolic risk factors, adipose tissue inflammation or gut permeability. While HC-24 did not affect total liver steatosis, there was a pronounced reduction in lobular inflammation in HC-24-treated animals, which was associated with modulation of genes involved in inflammation (e.g. neutrophil chemokine Cxcl1) and cholesterol homeostasis (i.e. predicted effect on 'cholesterol' as an upstream regulator, based on gene expression changes associated with cholesterol handling). These effects were confirmed by immunohistochemical staining of neutrophils and biochemical analysis of hepatic free cholesterol content. Intrahepatic free cholesterol levels were found to correlate significantly with the number of inflammatory aggregates in the liver, thereby providing a potential rationale for the observed anti-inflammatory effects of HC-24. Conclusions: Free cholesterol accumulates in the liver of Ldlr-/-.Leiden mice under physiologically translational dietary conditions, and this is associated with the development of hepatic inflammation. The multicomponent medicine HC-24 reduces accumulation of free cholesterol and has molecular and cellular anti-inflammatory effects in the liver.
2021-03-01 | GSE163652 | GEO
Project description:Tumors use various strategies for immune evasion. Understanding the mechanisms by which tumors suppress anti-tumor immunity facilitates the development of immunotherapies. Here we have identified tumor-secreted fibroblast growth factor 21 (FGF21) as an essential immune suppressor. We show that FGF21 is upregulated in multiple types of tumors and promotes tumor progression. FGF21 significantly disrupts CD8+T anti-tumor immune response by rewiring cholesterol metabolism of CD8+ T cells. We further reveal that FGF21 activates AKT-mTORC1- sterolregulatoryelementbindingprotein 1 (SREBP1) signal axis to enhance cholesterol biosynthesis in CD8+T cells. FGF21 knockdown or blockade of FGF21 by a neutralizing antibody attenuates AKT-mTORC1 signaling and subsequently decreases cholesterol content in CD8+T cells, thus restoring CD8+T cytotoxic function and robustly suppressing tumor growth. Our findings uncover FGF21 as a “secreted immune checkpoint” to restrict anti-tumor immunity and suggest its inhibition is a useful strategy for improving the efficacy of cancer immunotherapy.
2024-06-29 | GSE236180 | GEO
Project description:Cancer-cell-secreted miR-9-5p regulates cholesterol homeostasis to promote tumor metastasis [TF TB Rab27AKD miR-9KO]
| PRJNA923246 | ENA
Project description:Therapies targeting estrogenic stimulation in estrogen receptor positive (ER+) breast cancer (BC) reduce mortality, but resistance remains a major clinical problem. Molecular studies have shown few high frequency mutations to be associated with endocrine resistance. In contrast, expression profiling of primary ER+ BC samples has identified several promising signatures/networks for targeting. In this study, the cholesterol biosynthesis pathway was the common upregulated pathway in the ER+ LTED but not ER- LTED cell lines, suggesting a potential mechanism dependent on continued ER expression. Targeting the individual genes of the cholesterol biosynthesis pathway with siRNAs caused a 30-50% drop in proliferation. Further analysis showed increased expression of 25-hydroxycholesterol (HC) in the MCF7 LTED cells. Exogenous 25-HC or 27-HC increased ER mediated-transcription and expression of the endogenous estrogen-regulated gene TFF1 in ER+ LTED cells but not in the ER-negative LTED. Additionally, recruitment of the ER and CREB-binding protein (CBP) to the TFF1 promoter was increased upon treatment with 25-HC and 27-HC. In silico analysis of 704 primary ER+ BC patients treated with adjuvant tamoxifen showed increased expression of MSMO1 (p=0.047), EBP (p=0.043), SQLE (p=0.000009), and IDI1 (p=0.0005), enzymes required for cholesterol synthesis and increased in our in vitro models of endocrine resistance, to be associated with poor relapse-free survival. In contrast, no association was identified in over 700 patients with ER-negative BC. Taken together, these data provide support for the role of cholesterol biosynthesis enzymes and the cholesterol metabolites, 25-HC and 27-HC, in a novel mechanism of resistance to endocrine therapy in ER+ BC that has potential as a therapeutic target.
2016-05-20 | GSE75971 | GEO
Project description:Characterization of three hepatocyte cell lines (2 parental and 1 clone), under two different media conditions. Parental cell lines HepG2 and HC-04, single cell cloned from HC-04 defined as HC-04.J7. The goal of the project initially was to investigate the invasion of hepatocytes by Plasmodium falciparum sporozoites, and once found that the HC-04 cell had a higher invasion than HepG2, single cell isolates were generated from HC-04 before being expanded. The resulting HC-04.J7 isolate further improved the invasion rate. Transcriptomic and proteomic data sets were generated from all cell lines in both media, than analyzed for potential receptors or biochemical pathways that play a role in the increased invasion of HC-04 and specifically, HC-04.J7.
2019-11-12 | PXD008613 | Pride
Project description:High cholesterol diet and xenobiotic treatment induce changes in cholesterol homeostasis and drug metabolism. Mice were either 7 days on high cholesterol diet or were treated with phenobarbital. Liver samples were analyzed using Sterolgene v0 cDNA microarrays. Sterolgene microarray is a tool designed to enable focused studies of cholesterol homeostasis and drug metabolism. We show that one week of cholesterol diet down-regulates cholesterol biosynthesis and up-regulates xenobiotic metabolism (Cyp3 family). Phenobarbital treatment also up-regulates xenobiotic metabolism (Cyp2b and Cyp3a families). We can conclude that the Sterolgene series of cDNA microarrays represent novel original tool, enabling focused and cost-wise studies of cholesterol homeostasis and drug metabolism. Keywords: Treatment and diet effects One group of mice was treated i.p. with 50 mg/kg of phenobarbital in vehicle (5% DMSO in corn oil). Untreated group was injected vehicle. Third group was 7 days on 1 % (w/w) cholesterol diet prior vehicle treatment. After 10 h animals were sacrificed and livers were stored. Pools of total RNA from two animals were mixed. Three pools of untreated and phenobarbital treated groups, and two pools of cholesterol diet group were co-hybridized with liver reference on Sterolgene v0 cDNA microarray. No dye-swaps were performed.
2010-05-25 | E-GEOD-6447 | biostudies-arrayexpress
Project description:Bacillus subtilis strain:HC-9 | isolate:HC-9 Genome sequencing
| PRJNA1086793 | ENA
Project description:High cholesterol diet and xenobiotic treatment induce changes in cholesterol homeostasis and drug metabolism. Mice were either 7 days on high cholesterol diet or were treated with phenobarbital. Liver samples were anayzed using Affymetrix GeneChip MOE430A. Experiment Overall Design: One group of mice was treated 50 mg/kg of phenobarbital in vehicle (5% DMSO in corn oil). Untreated group was injected vehicle only. Third group was 7 days on 1% (w/w) cholesterol diet prior vehicle treatment. After 10 hours animals were sacrificed and total RNA was isolated from liver. Total RNA from two animals was pooled resulting in 4 pools per group. These pools were analyzed using Affymetrix GeneChip MOE430A.
2008-06-15 | E-GEOD-6721 | biostudies-arrayexpress