Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Deficiency of histone methyltransferase SETD2 in liver leads to abnormal lipid metabolism and hepatocarcinoma [ChIP-Seq]

ABSTRACT: H3K36me3 catalyzed by histone methyltransferase SETD2 is one of the most conserved epigenetic marks from yeast to mammals. SETD2 is frequently mutated in multiple cancers and acts as a tumor suppressor. Here, utilizing a liver-specific deletion of Setd2 mice model, we found that Setd2 depletion is sufficient to trigger hepatocarcinoma (HCC) spontaneously. Meanwhile, in a DEN-induced HCC model, Setd2 depletion significantly promoted tumor number and size. The mechanistic study showed that Setd2 suppresses HCC not only through modulating DNA damage response, but also regulating lipid metabolism in liver. Setd2 deficiency down-regulated the expression of cholesterol efflux genes and caused lipid accumulation. ChIP-Seq analysis further revealed that Setd2 deletion induced AP-1 activation in liver, which was probably trigged by accumulated cholesterol. AP-1 is a well-known oncogene in HCC and inhibits p53 in Setd2-deficient cells. Taken together, we found the role of an important epigenetic gene in regulating cholesterol homeostasis and HCC, and revealed the underlying mechanisms.

ORGANISM(S): Mus musculus

PROVIDER: GSE136743 | GEO | 2021/09/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Deficiency of histone methyltransferase SETD2 in liver leads to abnormal lipid metabolism and hepatocarcinoma [RNA-Seq]

Project description:H3K36me3 catalyzed by histone methyltransferase SETD2 is one of the most conserved epigenetic marks from yeast to mammals. SETD2 is frequently mutated in multiple cancers and acts as a tumor suppressor. Here, utilizing a liver-specific deletion of Setd2 mice model, we found that Setd2 depletion is sufficient to trigger hepatocarcinoma (HCC) spontaneously. Meanwhile, in a DEN-induced HCC model, Setd2 depletion significantly promoted tumor number and size. The mechanistic study showed that Setd2 suppresses HCC not only through modulating DNA damage response, but also regulating lipid metabolism in liver. Setd2 deficiency down-regulated the expression of cholesterol efflux genes and caused lipid accumulation. ChIP-Seq analysis further revealed that Setd2 deletion induced AP-1 activation in liver, which was probably trigged by accumulated cholesterol. AP-1 is a well-known oncogene in HCC and inhibits p53 in Setd2-deficient cells. Taken together, we found the role of an important epigenetic gene in regulating cholesterol homeostasis and HCC, and revealed the underlying mechanisms.

2021-09-01 | GSE136742 | GEO

Deficiency of histone methyltransferase SETD2 in liver leads to abnormal lipid metabolism and hepatocarcinoma

Project description:Deficiency of histone methyltransferase SETD2 in liver leads to abnormal lipid metabolism and hepatocarcinoma

| PRJNA563558 | ENA

A novel MYC-ZNF706-SLC7A11 regulatory circuitry contributes to cancer progression and redox balance in human hepatocarcinoma (ChIP-Seq)

Project description:ZNF706 belongs to a member of C2H2-type zinc finger proteins which exerts pivotal roles in cancer progression. However, the biological function and mechanism of ZNF706 are rarely investigated. Using qRT-PCR and Western blot assays, we identified ZNF706 was frequently amplified in human hepatocarcinoma and high ZNF706 expression was associated with unfavorable HCC patient survival based on TCGA database. In vitro and in vivo experiments revealed that ZNF706 promoted HCC cell growth. Mechanistically, RNA-seq and ChIP-seq identified SLC7A11 was a critical target of ZNF706, and depletion of ZNF706 increased lipid peroxidation, cell death and decreased cystine uptake medicated by SLC7A11 contributing to redox homeostasis disruption. Furthermore, using luciferase report assays and ChIP-qPCR, we found MYC could regulate ZNF706 transcription by binding to ZNF706 promoter region, and further assay indicated MYC also involved in redox balance by modulating SLC7A11. Collectively, our study uncovers that the oncogenic role of ZNF706 in liver cancer, indicating that ZNF706 inhibition could be a potential treatment strategy for liver cancer.

2024-06-17 | GSE246331 | GEO

A novel MYC-ZNF706-SLC7A11 regulatory circuitry contributes to cancer progression and redox balance in human hepatocarcinoma (RNA-Seq)

2024-06-17 | GSE246330 | GEO

Deficiency of histone methyltransferase SETD2 in liver leads to abnormal lipid metabolism and hepatocarcinoma [RNA-Seq]

Project description:Deficiency of histone methyltransferase SETD2 in liver leads to abnormal lipid metabolism and hepatocarcinoma [RNA-Seq]

| PRJNA563560 | ENA

Deficiency of histone methyltransferase SETD2 in liver leads to abnormal lipid metabolism and hepatocarcinoma [ChIP-Seq]

Project description:Deficiency of histone methyltransferase SETD2 in liver leads to abnormal lipid metabolism and hepatocarcinoma [ChIP-Seq]

| PRJNA563561 | ENA

Cell-permeated peptide P-T3H2 inhibits malignancy on hepatocarcinoma through stabilizing HNF4α protein

Project description:Objectives: Hepatocyte nuclear factor 4α (HNF4α) is a key regulator of hepatocyte function and has a strong therapeutic effect on hepatocellular carcinoma (HCC) by inducing the differentiation of hepatoma cell into hepatocytes. Our previous study showed that Tribbles homolog 3 (TRIB3) directly interacts with and promotes the degradation of HNF4α in non-alcoholic fatty liver disease (NAFLD). Disrupting the TRIB3-HNF4α interaction by using a cell-permeating peptide called P-T3H2 stabilizes HNF4α protein. This study aimed to assess the anti-tumor impact of P-T3H2 in HCC. Methods: The expression of TRIB3 and HNF4α was assessed using western blot and immunohistochemistry staining (IHC). Hepatic functions in HCC cells were evaluated through periodic acid-Schiff (PAS) staining and acetylated low-density lipoprotein (ac-LDL) uptake. Senescence-associated β-galactosidase (SA-β-gal) activity staining was used to detected the cellular senescence in HCC cells. RNA-Seq analysis was carried out to identify differentially expressed genes in Huh-7 cells treated with the peptide P-T3H2 compared to the control peptide P-T3H2-2A. The impact of P-T3H2 on hepatocarcinoma malignancy was evaluated in HCC cells, a Huh-7 xenograft mouse model, an orthotopic model, and a C-MET/ΔN90-β-catenin-driven HCC model. Results: TRIB3 exhibited a negative correlation with HNF4α in both human and mouse HCC tissues. The administration of P-T3H2 significantly inhibited the malignancy of HCC cells. Additionally, P-T3H2 stabilized the HNF4α protein and facilitated the restoration of hepatic functions and the cellular senescence in HCC cells. RNA-Seq analysis demonstrated that P-T3H2 enhanced the transcriptional activity of HNF4α in HCC. Furthermore, P-T3H2 effectively suppressed the growth of HCC tumors in both of the Huh7 xenograft and orthotopic mouse models in vivo. Notably, P-T3H2 also inhibits hepatocarcinogenesis in the C-MET/ΔN90-β-catenin-driven HCC model.

2024-12-18 | GSE260862 | GEO

PRDX6 as a promoter of cancer malignancy in hepatocarcinoma cell lines targeting GSK3B

Project description:This project describes the mechanism by wich PRDX6 affects migration and invasiveness in hepatocarcinoma cells. SNU475 (mesenchymal) hepatocarcinoma cell line knockout for PRDX6 showed a marked increase in ROS and lipid peroxidation, mytochondrial dysfunction, metabolic reprogramming, altered cytoskeleton and activation of upstream regulators MYC, ATF4, HNF4A and HNF4G and inhibition of NRF2 and TP53. All these changes point to a role of PRDX6 in tumor development pointing to it as a candidate for antitumoral therapies.

2023-07-20 | PXD039491 | Pride

Human hepatocarcinoma cells : Huh-7 vs. SNU-739

Project description:Transcriptional profiling of human hepatocarcinoma comparing Huh-7 and SNU-739.

2014-04-29 | GSE57106 | GEO

Gene expression in PBMCs of patients with hepatocarcinoma: effect of ablative treatment - genes

Project description:Gene expression profiles of PBMCs in patients with hepatocarcinoma after ablative treatment. Results provide the information of changes in PBMPs transcriptome following ablative treatment of hepatocarcinoma.

2020-01-04 | GSE143004 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data