Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Pancreatic cancer cells require the transcription factor MYRF (Myelin Regulatory Factor) to maintain ER homeostasis (RNA-Seq).

ABSTRACT: Many tumors of endodermal origin are composed of highly secretory cancer cells that must adapt endoplasmic reticulum (ER) activity to enable proper folding of secretory proteins, prevent ER stress and thus maintain their viability. In pancreatic ductal adenocarcinoma (PDAC), well-differentiated and secretory cancer cells coexist with poorly differentiated cells with quasi-mesenchymal features. We found that the differentiated PDAC cells, but not the undifferentiated ones, expressed an ER membrane-associated transcription factor (TF), Myelin Regulatory Factor (MYRF), that is released by self-cleavage and translocates to the nucleus. MYRF expression was directly controlled by HNF1B, a TF maintaining epithelial identity in PDAC, and it acted to fine-tune the expression of genes encoding highly glycosylated and cysteine-rich secretory proteins, thus preventing ER overload. MYRF-deficient PDAC cells showed anatomical and biochemical signs of ER stress, impaired proliferation and inability to form spheroids in vitro, while in vivo they generated highly secretory but poorly proliferating and hypo-cellular tumors. These data indicate a role of MYRF in the control of homeostasis and proliferation of cancer cells with high secretory activity

ORGANISM(S): Homo sapiens

PROVIDER: GSE145628 | GEO | 2020/09/18

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Pancreatic cancer cells require the transcription factor MYRF (Myelin Regulatory Factor) to maintain ER homeostasis (ChIP-Seq).

Project description:Many tumors of endodermal origin are composed of highly secretory cancer cells that must adapt endoplasmic reticulum (ER) activity to enable proper folding of secretory proteins, prevent ER stress and thus maintain their viability. In pancreatic ductal adenocarcinoma (PDAC), well-differentiated and secretory cancer cells coexist with poorly differentiated cells with quasi-mesenchymal features. We found that the differentiated PDAC cells, but not the undifferentiated ones, expressed an ER membrane-associated transcription factor (TF), Myelin Regulatory Factor (MYRF), that is released by self-cleavage and translocates to the nucleus. MYRF expression was directly controlled by HNF1B, a TF maintaining epithelial identity in PDAC, and it acted to fine-tune the expression of genes encoding highly glycosylated and cysteine-rich secretory proteins, thus preventing ER overload. MYRF-deficient PDAC cells showed anatomical and biochemical signs of ER stress, impaired proliferation and inability to form spheroids in vitro, while in vivo they generated highly secretory but poorly proliferating and hypo-cellular tumors. These data indicate a role of MYRF in the control of homeostasis and proliferation of cancer cells with high secretory activity

2020-09-18 | GSE145627 | GEO

RNA Sequencing Analysis of Wild Type and Myrf +/− mice Retina

Project description:We have created a Myrf knockdown (Myrf +/−) mutant mouse strain and investigated the molecular phenotype of reduced MYRF expression in the retina using RNA-sequencing. As an initial finding, photoreceptor defects with impaired functions of spatial vision and retinal electrophysiology were found in Myrf +/− mice, indicating an important role of MYRF in retinal development.It was revealed through RNA-seq that the expression of phototransduction and estrogen signaling pathways reduced in Myrf +/− mice. Thus, alterations of phototransduction and estrogen signaling pathways seem to play important roles in connecting Myrf deficiency with retinal photoreceptor defects.

2020-09-12 | GSE157806 | GEO

Pancreatic cancer cells require the transcription factor MYRF (Myelin Regulatory Factor) to maintain ER homeostasis

Project description:Pancreatic cancer cells require the transcription factor MYRF (Myelin Regulatory Factor) to maintain ER homeostasis

| PRJNA607766 | ENA

Comparative MicroRNA Sequencing Analysis in Late L1 Larvae of C. elegans: Wild Type N2 Versus myrf-1(ju1121) Mutants

Project description:Our research revealed that the transmembrane transcription factors MYRF-1 and MYRF-2 are crucial for activating the microRNA lin-4 at the end of the first larval stage in C. elegans. To determine whether MYRF regulates other microRNA genes during this period, we conducted a microRNA sequencing analysis to compare microRNA expression in late L1 larvae of wild type and myrf-1(ju1121) mutants. The myrf-1(ju1121) mutation causes a loss of function in both MYRF-1 and MYRF-2. Our analysis identified a subset of microRNAs that were differentially expressed between the wild type and the myrf-1(ju1121) mutants.

2024-03-31 | GSE262766 | GEO

Pancreatic cancer cells require the transcription factor MYRF (Myelin Regulatory Factor) to maintain ER homeostasis (ChIP-Seq).

Project description:Pancreatic cancer cells require the transcription factor MYRF (Myelin Regulatory Factor) to maintain ER homeostasis (ChIP-Seq).

| PRJNA607770 | ENA

Pancreatic cancer cells require the transcription factor MYRF (Myelin Regulatory Factor) to maintain ER homeostasis (RNA-Seq).

Project description:Pancreatic cancer cells require the transcription factor MYRF (Myelin Regulatory Factor) to maintain ER homeostasis (RNA-Seq).

| PRJNA607769 | ENA

Microarray expression profiling study of Runx1-null and wild type luminal mammary epithelial cells

Project description:RUNX1 encodes a RUNX family transcription factor (TF) and was recently identified as a novel mutated gene in human luminal breast cancers. We found that Runx1 is expressed in all subpopulations of murine mammary epithelial cells (MECs) except the secretory alveolar luminal cells. Conditional knockout of Runx1 in MECs by MMTV-Cre led to a decrease in luminal MECs, largely due to a profound reduction in the estrogen receptor (ER)-positive mature luminal subpopulation, a phenotype that could be rescued by loss of either Trp53 or Rb1. Mechanistically RUNX1 represses Elf5, a master regulatory TF gene for alveolar cells, and activates Foxa1, a key mature luminal TF gene involved in the ER program. Collectively, our data identified a key regulator of the ER+ luminal lineage whose disruption may contribute to development of ER+ luminal breast cancer when under the background of either TP53 or RB1 loss.

2014-11-26 | GSE47375 | GEO

Subtypes in human pancreatic ductal adenocarcinoma based on niche factor dependency show distinct drug treatment responses

Project description:BACKGROUND & AIMS: Pancreatic ductal adenocarcinoma (PDAC) is characterized by abundant stroma in which microenvironmental (niche) factors promote PDAC progression. In mouse models, reduction of the stroma increased the proportion of poorly differentiated PDAC with a worse prognosis. Here, we aimed to clarify the effects of stroma on PDAC that may define the PDAC phenotype and induce distinct therapeutic responses. METHODS: The molecular features of PDAC based on differentiation grade were clarified by genome and transcriptome analysis using PDAC organoids (PDOs). We identified the dependency on niche factors that might regulate the differentiation grade. A three-dimensional co-culture model with cancer-associated fibroblasts (CAFs) was generated to determine whether CAFs provide niche factors essential for differentiated PDAC. PDOs were subtyped based on niche factor dependency, and the therapeutic responses for each subtype were compared. RESULTS: The expression profiles of PDOs differed depending on the differentiation grade. Consistent with the distinct profiles, well differentiated types showed high niche dependency, while poorly differentiated types showed low niche dependency. The three-dimensional co-culture model revealed that well differentiated PDOs were strongly dependent on CAFs for growth, and moderately differentiated PDOs showed plasticity to change morphology depending on CAFs. Differentiated PDOs upregulated the expression of mevalonate pathway-related genes correlated with the niche dependency and were significantly more sensitive to simvastatin than poorly differentiated PDOs. CONCLUSIONS: Our findings suggest that CAFs maintain the differentiated PDAC phenotype through secreting niche factors and induce distinct drug responses. These results may lead to the development of novel subtype-based therapeutic strategies.

2021-08-07 | GSE181593 | GEO

Interferon regulatory factor 1 (IRF1) controls the metabolic programmes of low-grade pancreatic cancer cells (ChIP-Seq)

Project description:Pancreatic ductal adenocarcinomas (PDACs) are composed of a mixture of highly heterogeneous cancer cells with distinct gene expression programs and functional properties, ranging from well-differentiated (low-grade) epithelial cells forming pseudo-glandular structures, to undifferentiated (high-grade) quasi-mesenchymal cells. Low-grade, differentiated PDAC cells are characterized by the constitutive expression of many Interferon (IFN)-stimulated genes (ISGs) but the mechanistic bases and the functional implications of this property are unknown. Here we show that constitutive ISG expression as well as responsiveness to IFN stimulation depend on the maintenance of high expression levels of the transcription factor IRF1 (Interferon Regulatory Factor 1) by epithelial lineage-determining transcription factors. IRF1-dependent gene expression provides differentiated PDAC cells with a range of distinctive properties related to antigen presentation and processing and maintenance of epithelial identity, as well as a distinctive metabolic program in which both mitochondrial respiration and fatty acid synthesis are directly suppressed

2022-05-09 | GSE165947 | GEO

Interferon regulatory factor 1 (IRF1) controls the metabolic programmes of low-grade pancreatic cancer cells (ATAC-Seq)

2022-05-09 | GSE165946 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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