Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

ZDHHC12 palmitoylates HDAC8 and promotes the development of hepatocellular carcinoma associated with a diet high in saturated fatty acids

ABSTRACT: Excessive intake of saturated fatty acids (SFAs), which are prevalent in diets high in fried foods and red meat, poses a significant threat for hepatocellular carcinoma (HCC). Herein, we found via Mendelian randomization (MR) analysis that SFAs could be one of the factors leading to HCC. However, the role and associated mechanism of SFAs in HCC progression remain poorly understood. Palmitic acid (PA) is the most common type of SFA. We therefore chose PA as an example of SFAs for our study. We identified zinc finger DHHC-type palmitoyltransferase 12 (ZDHHC12) as a key protein involved in the promotion of HCC progression by PA, which was accomplished by maintaining the stability of the recognized HCC-promoting gene histone deacetylase 8 (HDAC8). Mechanistically, supplementation with PA led to the upregulation of ZDHHC12 expression via activation of the transcription factor SWI/SNF-related BAF chromatin remodeling complex subunit ATPase 4 (SMARCA4). ZDHHC12 mediated the palmitoylation of HDAC8 at cysteine 244, thereby preventing the lysosomal degradation of HDAC8, which promoted the progression of HCC. In conclusion, this study revealed that ZDHHC12 was a key protein in palmitic acid-mediated HCC progression and that targeting HDAC8 could inhibit this process. These findings offer a potential therapeutic strategy for HCC patients with a high intake of saturated fatty acids, especially palmitic acid.

ORGANISM(S): Homo sapiens

PROVIDER: GSE290907 | GEO | 2025/12/03

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Transcriptional profiles reveal deregulation of lipid metabolism and inflammatory pathways in neurons exposed to palmitic acid

Project description:The effects of the consumption of high-fat diets (HFD) have been studied to unravel the molecular pathways they are altering in order to understand the link between increased caloric intake, metabolic diseases, and the risk of cognitive dysfunction. The saturated fatty acid, palmitic acid (PA), is the main component of HFD and it has been found increased in the circulation of obese and diabetic people. In the central nervous system, PA has been associated with inflammatory responses in astrocytes, but the effects on neurons exposed to PA have not been largely investigated. Given that PA affect a variety of metabolic pathways, we aimed to analyze the genomic profile activated by this fatty acid to shed light on the mechanisms of neuronal dysfunction. In the current study, we profiled the transcriptome response after PA exposition at non-toxic doses in primary hippocampal neurons. Gene ontology and Reactome analysis revealed a pattern of gene expression which is associated with inflammatory pathways and, importantly, with the activation of lipid metabolism that is considered not very active in neurons. Validation by qRT-PCR of Hmgcs2, Angptl4, Ugt8 and Rnf145 confirmed the results obtained by RNAseq. Overall, these findings suggest that neurons are able to respond to saturated fatty acids changing the expression pattern of genes associated with inflammatory response and lipid utilization that may be involved in the neuronal damage associated with metabolic diseases

2022-03-01 | GSE166985 | GEO

The Effect of Fatty Acids in Hepatic Insulin Resistance - Part 1

Project description:Monounsaturated fatty acid (MUFA) oleic acid (OA) has been reported to restore saturated fatty acid palmitic acid (PA)-induced hepatic insulin resistance (IR). However, the detailed molecular mechanism remains elusive. In addition, -3 polyunsaturated fatty acid (PUFA) such as Eicosapentaenoic acid (EPA) has also exerted opposite effects to PA in muscle IR. But whether it plays the same role in hepatic IR and the possible mechanism involved needs to be further explored. Here, we compared the proteome change of HepG2 cells after different fatty acids treatment.

2019-07-11 | PXD012065 | Pride

Gene expression data from differentiated 3T3-L1 preadipocytes treated with Palmitic Acid, Stearic Acid, Palmitoleic Acid, or Oleic Acid

Project description:Saturated fatty acids (SFA) are widely thought to induce inflammation in adipose tissue (AT), while monounsaturated fatty acids (MUFA) are purported to have the opposite effect; however, it is unclear if individual SFA and MUFA behave similarly. Our goal was to examine adipocyte transcriptional networks regulated by individual SFA (palmitic acid, PA; stearic acid, SA) and MUFA (palmitoleic acid, PMA; oleic acid, OA). Global gene expression was examined in differentiated preadipocytes treated with either 250 μM PA, SA, PMA, or OA for 48 hrs. Individual fatty acid treatments had significant effects on adipocyte gene expression. Functional analyses revealed that PA induced the TLR signalling pathway, while PMA had the opposite effect. SA and OA had similar effects, with increases in key metabolic pathways including mTOR and PPAR signalling, and a reduction in TLR signalling. Ccl5 was validated as a candidate gene that may mediate the differential inflammatory effects of SFA and MUFA in AT. Individual SFA and MUFA trigger distinct transcriptional responses in differentiated preadipocytes, with inflammatory and metabolic pathways particularly sensitive to these fatty acids.

2012-11-13 | GSE42220 | GEO

Gene expression data from differentiated 3T3-L1 preadipocytes treated with Palmitic Acid, Stearic Acid, Palmitoleic Acid, or Oleic Acid

Project description:Saturated fatty acids (SFA) are widely thought to induce inflammation in adipose tissue (AT), while monounsaturated fatty acids (MUFA) are purported to have the opposite effect; however, it is unclear if individual SFA and MUFA behave similarly. Our goal was to examine adipocyte transcriptional networks regulated by individual SFA (palmitic acid, PA; stearic acid, SA) and MUFA (palmitoleic acid, PMA; oleic acid, OA). Global gene expression was examined in differentiated preadipocytes treated with either 250 M-NM-<M PA, SA, PMA, or OA for 48 hrs. Individual fatty acid treatments had significant effects on adipocyte gene expression. Functional analyses revealed that PA induced the TLR signalling pathway, while PMA had the opposite effect. SA and OA had similar effects, with increases in key metabolic pathways including mTOR and PPAR signalling, and a reduction in TLR signalling. Ccl5 was validated as a candidate gene that may mediate the differential inflammatory effects of SFA and MUFA in AT. Individual SFA and MUFA trigger distinct transcriptional responses in differentiated preadipocytes, with inflammatory and metabolic pathways particularly sensitive to these fatty acids. A total of 4 microarrays were run for each FA treatment. We experienced difficulties with the cRNA amplification for one replicate from the OA treated cells; therefore this treatment group only had an n=3. For each sample, 100 ng of total RNA was prepared for hybridization to Affymetrix Mouse Gene 1.1 ST array strips, according to the manufacturerM-bM-^@M-^Ys instructions (Affymetrix Inc., Fremont, CA, USA).

2012-11-13 | E-GEOD-42220 | biostudies-arrayexpress

Early growth response protein-1 coordinates lipotoxicity-associated placental inflammation: Role in Maternal Obesity

Project description:Maternal obesity during pregnancy leads to a pro-inflammatory milieu in the placenta. We conducted a global transcriptomic profiling in BeWo cells following palmitic acid (PA, 500 uM) and/or TNF-alpha (10 ng/ml) treatment for 24 h. Microarray analysis revealed that placental cytotrophoblasts increased expression of genes related to inflammation, stress response and immediate-early factors in response to plamitic acid, TNF-alpha or a combination of both. Our results suggest that fatty acids and inflammatory cytokines induce inflammation in placental cells via activation of JNK-Egr-1 signaling. global transcriptomic profiling in BeWo cells following palmitic acid (PA, 500 uM) and/or TNF-alpha (10 ng/ml) treatment for 24 h

2014-01-21 | E-GEOD-43685 | biostudies-arrayexpress

Palmitic Acid Upregulates Type I Interferon-Mediated Antiviral Response and Cholesterol Biosynthesis in Human Astrocytes

Project description:Chronic intake of a high-fat diet increases saturated fatty acids in the brain causing the progression of neurodegenerative diseases. Palmitic acid is a free fatty acid abundant in the diet that at high concentrations may penetrate the blood brain barrier and stimulate the production of pro-inflammatory cytokines, leading to inflammation in astrocytes. The use of the synthetic neurosteroid tibolone in protection against fatty acid toxicity is emerging, but its transcriptional effects on palmitic acid induced lipotoxicity remain unclear. Herein, we performed a transcriptome profiling of normal human astrocytes to investigate the molecular mechanisms by which palmitic acid causes cellular damage to astrocytes, and whether tibolone could reverse its detrimental effects. Astrocytes undergo a profound transcriptional change at 2 mM palmitic acid, affecting the expression of 739 genes, 366 upregulated and 373 downregulated. However, tibolone at 10 nM does not entirely reverse palmitic acid effects. Additionally, the protein protein interaction reveals two novel gene clustering modules. The first module involves astrocyte defense responses by upregulation of pathways associated with antiviral innate immunity, and the second is linked to lipid metabolism. Our data suggest that activation of viral response signaling pathways might be so far, the initial molecular mechanism of astrocytes in response to a lipotoxic insult by palmitic acid, triggered particularly upon increased expression levels of *IFIT2*, *IRF1*, and *XAF1*. Therefore, this novel approach using a global gene expression analysis may shed light on the pleiotropic effects of palmitic acid on astrocytes, and provide a basis for future studies addressed to elucidate these responses in neurodegenerative conditions, which is highly valuable for the design of therapeutic strategies.

2021-02-10 | GSE166500 | GEO

Palmitate-induced gene expression in human gingival fibroblasts (HGF)

Project description:DNA microarray analysis was performed to investigate the expression of genes in HGF stimulated with palmitate Type 2 diabetes (T2D) is characterized by decreased insulin sensitivity and higher concentrations of free fatty acids (FFAs) in plasma. Among FFAs, saturated fatty acids (SFAs), such as palmitate, have been proposed to promote inflammatory responses. Although many epidemiological studies have shown a link between periodontitis and T2D, little is known about the clinical significance of SFAs in periodontitis. The goal of this study is to demonstrate a potential link between the pathogenesis of periodontitis and SFAs in plasma.

2015-12-31 | GSE62761 | GEO

Palmitate-induced gene expression in human gingival fibroblasts (HGF)

2015-12-31 | E-GEOD-62761 | biostudies-arrayexpress

Endoplasmic reticulum stress sensor protein PERK in hepatic stellate cells promotes the progression of hepatocellular carcinoma via p38δ MAPK/IL-1β axis

Project description:Palmitic acid (PA) absorption from the intestine is increased in metabolic dysfunction-associated steatohepatitis (MASH). It induces endoplasmic reticulum (ER) stress and interleukin-1 beta (IL-1β) production in hepatic stellate cells (HSCs). Protein kinase R-like endoplasmic reticulum kinase (PERK) is an ER stress sensor protein involved in HSC activation and liver fibrosis. However, its role in HSCs during hepatocellular carcinoma (HCC) progression remains unclear. This study clarified the process of IL-1β production via PERK in HSCs and explored the mechanism underlying MASH-related HCC progression. HSCs were treated with PA or transfected with PERK small-interfering RNA (siRNA) or PERK plasmid. Proliferation, scratch, and Transwell assays were performed on HCC cells cultured in the conditioned medium (CM) from HSCs. PA treatment increased PERK and IL-1β expressions in HSCs. PERK knockdown decreased IL-1β expression, while its overexpression increased it in HSCs. The CM from PA-treated HSCs showed elevated IL-1β levels and enhanced HCC cells’ proliferation, migration, and invasion; however, these effects were suppressed by PERK knockdown in HSCs. RNA-sequencing analysis revealed that p38δ mitogen-activated protein kinase (MAPK) is the intermediate molecule between PERK and IL-1β in HSCs. In the tumor microenvironment of MASH-related HCC, PERK in HSCs promotes HCC progression via the p38δ MAPK/IL-1β axis.

2025-06-07 | GSE292002 | GEO

Expression data from fatty acid and bile acid receptor agonist treated liver sinusoidal endothelial cells

Project description:Liver sinusoidal endothelial cells (LSEC) are unique endothelial cell typelining the sinusoids of the liver and we have shown that these cells respond in a unique matter when exposed to saturated and unsaturated free fatty acids (FFA) and bile acids. We used microarray to analyze the transcriptional differences between the LSEC exposed to free fatty acids and bile acid receptor agonists to further shed light on their role in non-alcoholic fatty liver disease. The Murine Liver Sinusoidal Endothelial Cell Line (TSEC) was treated with palmitic and oleic acid or the bile acid receptor agonist INT-767 for 8 hours. Total RNA was then harvested to determine transcriptional differences.

2015-05-07 | E-GEOD-67651 | biostudies-arrayexpress

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