Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

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

PROVIDER: PRJNA1236308 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR32699728.fastq.gz	Fastqsanger.gz
	SRR32699729.fastq.gz	Fastqsanger.gz
	SRR32699730.fastq.gz	Fastqsanger.gz
	SRR32699731.fastq.gz	Fastqsanger.gz
	SRR32699732.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 6

Similar Datasets

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

The eIF2 kinase PERK and the integrated stress response facilitate activation of ATF6 during endoplasmic reticulum stress

Project description:Disruptions of the endoplasmic reticulum (ER) that perturb protein folding cause ER stress and elicit an unfolded protein response (UPR) that involves translational and transcriptional changes in gene expression aimed at expanding the ER processing capacity and alleviating cellular injury. Three ER stress sensors PERK, ATF6, and IRE1 implement the UPR. PERK phosphorylation of eIF2 during ER stress represses protein synthesis, which prevents further influx of ER client proteins, along with preferential translation of ATF4, a transcription activator of the integrated stress response. In this study we show that the PERK/eIF2α~P/ATF4 pathway is required not only for translational control, but also activation of ATF6 and its target genes. The PERK pathway facilitates both the synthesis of ATF6 and trafficking of ATF6 from the ER to the Golgi for intramembrane proteolysis and activation of ATF6. As a consequence, liver-specific depletion of PERK significantly reduces both the translational and transcriptional phases of the UPR, leading to reduced protein chaperone expression, disruptions of lipid metabolism, and enhanced apoptosis. These findings show that the regulatory networks of the UPR are fully integrated, and helps explain the diverse pathologies associated with loss of PERK. 14 gene expression arrays, 3 WT control arrays; 3 lsPERK control arrays; 4 WT Treated arrays; 4 lsPERK treated arrays. Comparison of gene expression profiles for treated vs control in wildtype and knock-out.

2012-01-20 | E-GEOD-29929 | biostudies-arrayexpress

The eIF2 kinase PERK and the integrated stress response facilitate activation of ATF6 during endoplasmic reticulum stress

2012-01-20 | GSE29929 | GEO

Gene expression profiles of control or PERK siRNA-transfected brown adipocyte during the differentiation

Project description:The area of mitochondria in differentiated brown adipocytes is dramatically increased compared with that in brown pre-adipocytes. The ATP production is switched from the glycolysis pathway to the OXPHOS pathway during brown adipocyte differentiation. Endoplasmic reticulum (ER) is surrounded by mitochondria and the area of contact sites between mitochondria and the ER is increased. ER stress sensor PERK was phosphorylated during differentiation. To elucidate the mitochondria-ER crosstalk signaling mediated by PERK, RNA-sequencing analysis was performed using control siRNA- or PERK siRNA-transfected brown adipocytes.

2020-02-03 | GSE132598 | GEO

ER stress sensor PERK drives tumor-promoting myelopoiesis by reprogramming hematopoietic progenitor cells in the spleen

Project description:The spleen, as the prominent site for extramedullary myelopoiesis in cancer, generates significant amounts of myeloid cells to promote tumor progression. Cancer-associated splenic myelopoiesis is mediated by a population of functionally distinct hematopoietic stem/progenitor cells (HSPCs) that are committed to immunosuppressive myeloid cell generation, but the molecular mechanism regulating this response remains unclear. Here, we found that HSPCs in the spleen of tumor-bearing mice exhibited accelerated protein synthesis and engaged in a robust endoplasmic reticulum (ER) stress response. Single-cell RNA sequencing showed that the ER stress response was concomitant with the myeloid-biased lineage commitment and dysfunction of HSPCs in the spleen. PKR-like ER resident kinase (PERK), a molecular sensor of ER stress, directed HSPC differentiation into myeloid-derived suppressor cells (MDSCs) via PERK–eIF2α–ATF4–C/EBPβ signaling. Inhibition of this signaling prevented the emergence of granulocyte/macrophage colony-stimulating factor-expressing HSPCs in the spleen and disrupted the positive feedback-driven splenic myelopoiesis. Consequently, a blockade of PERK abated the suppressive function of tumor-infiltrating MDSCs and increased cytotoxic T cell infiltration, reshaping the tumor microenvironment to effectively suppress disease progression and potentiate both immuno- and targeted therapies. In accordance, activation of PERK–ATF4–C/EBPβ signaling was indispensable for the differentiation of human umbilical cord blood-derived HSPCs into functionally competent MDSCs. Together, these results indicate a crucial role for the cellular ER stress sensor PERK in modulating splenic HSPC activities in cancer, suggesting novel therapeutic opportunities for targeting the tumor-promoting myeloid response at its source. Raw data are available on Genome Sequence Archive, Bioproject accession number: PRJCA003519

2022-03-04 | GSE158486 | GEO

EP152R-Mediated Endoplasmic Reticulum Stress Contributes to African Swine Fever Virus Infection via the PERK-eIF2α Pathway

Project description:African swine fever virus (ASFV) is a large, icosahedral, double-stranded DNA virus in the Asfarviridae family and the causative agent of African swine fever (ASF). ASFV causes a hemorrhagic fever with high mortality rates in domestic and wild pigs. ASFV contains an open reading frame named EP152R, previous research has shown that EP152R is an essential gene for virusrescue in swine macrophages. However, the detailed functions of ASFV EP152R remain elusive. Herein, we demonstrate that EP152R, a membrane protein located in the endoplasmic reticulum (ER), induces ER stress and swelling, triggering the PERK/eIF2α pathway and broadly inhibiting host protein synthesis in vitro. Additionally, EP152R strongly promotes immune evasion, reduces cell proliferation, and alters cellular metabolism. These results suggest that ASFV EP152R plays a critical role in the intracellular environment, facilitating viral replication. Furthermore, virus-level experiments have shown that the knockdown of EP152R or PERK inhibitors efficiently affects viral replication by decreasing viral gene expression. In summary, these findings reveal a series of novel functions of ASFV EP152R and have important implications for understanding host-pathogen interactions.

2024-08-22 | GSE275101 | GEO

A stress sensor IRE1α is required for bacterial exotoxin-induced interleukin-1β production in tissue-resident macrophages

Project description:Cholera toxin (CT), a bacterial exotoxin composed of one A subunit (CTA) and five B subunits (CTB), functions as an immune adjuvant. CTB can induce production of interleukin-1β (IL-1β), a proinflammatory cytokine, in synergy with a lipopolysaccharide (LPS), from resident peritoneal macrophages (RPMs) through the pyrin and NLRP3 inflammasomes. However, how CTB or CT activates these inflammasomes in the macrophages has been unclear. Here, we clarified the roles of IRE1α , an endoplasmic reticulum (ER) stress sensor, in CT-induced IL-1β production from RPMs. In RPMs, CTB is incorporated into ER and induced ER stress responses, depending on GM1, a cell membrane ganglioside. IRE1α -deficient RPMs showed a significant impairment of CT- or CTB-induced IL-1β production, indicating that IRE1α was required for CT- or CTB-induced IL-1β production from RPMs. This study demonstrates the critical roles of IRE1α in activation of both NLRP3 and pyrin inflammasomes in tissue-resident macrophages.

2024-03-24 | GSE228915 | GEO

Noncanonical mRNA decay by the endoplasmic-reticulum stress sensor IRE1-alpha promotes cancer cell survival

Project description:Noncanonical mRNA decay by the endoplasmic-reticulum stress sensor IRE1-alpha promotes cancer cell survival

| PRJNA717050 | ENA

EP152R-Mediated Endoplasmic Reticulum Stress Contributes to African Swine Fever Virus Infection via the PERK-eIF2α Pathway

Project description:EP152R-Mediated Endoplasmic Reticulum Stress Contributes to African Swine Fever Virus Infection via the PERK-eIF2α Pathway

| PRJNA1149301 | ENA

Pharmacological induction of selective endoplasmic reticulum retention as a novel strategy for cancer therapy

Project description:We analysed the difference in the surface proteome of human cells that were either subjected to ER stress (induced by thapsigargin (Tg)) only or were additionally treated with a pharmacological inhibitor against the eIF2α kinase PERK, which is localized in the endoplasmic reticulum. Compared to single ER stress, several important plasma-membrane associated kinases, showed a significant downregulation under PERK inhibition.

2020-03-02 | PXD014709 | Pride

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