Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

ChIP-seq of β-Catenin in human hepatocellular carcinoma cells

ABSTRACT: Hypoxia is one of the main driving forces that results in poor outcomes and drug resistance in hepatocellular carcinoma (HCC). As the critical cellular oxygen sensor, mitochondria respond to hypoxic stress by sending retrograde signals to the nucleus that initiate adaptive metabolic responses and maintain the survival of HCC cells. Increasing evidence suggested autophagy contributes to sustain mitochondrial metabolic and quality control. Understanding how mitochondria communicate with the nucleus and alter transcription may provide promising targets for HCC treatment. In this study, we found mitochondrial undergoes selective degradation by autophagy under hypoxia. Furthermore, autophagy-activated HDAC6 not only promoted the nuclear translocation of b-catenin but also increased the affinity of b-catenin to the transcription repressor chicken ovalbumin upstream promoter-transcription factor 2 (COUP-TF II;), which suppressed mitochondrial oxidative phosphorylation-related genes transcription. Our data showed that autophagy served as a critical mediator of integrating mitochondrial energy metabolism and nuclear transcription. HDAC6 may be a potential target for reducing the survival of HCC cells by interrupting mitochondrial–nuclear crosstalk

ORGANISM(S): Homo sapiens

PROVIDER: GSE186801 | GEO | 2021/11/05

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

STAT6 in mitochondrial outer membrane impairs mitochondrial fusion by inhibiting MFN2 dimerization

Project description:Although it is reported that mitochondria-localized nuclear transcription factors (TFs) regulate mitochondrial processes such as apoptosis and mitochondrial transcription/respiration, their functions and mechanisms of mitochondrial dynamics regulated by mitochondria-localized nuclear TFs are yet to be fully characterized. Here, we identify STAT6 as a mitochondrial protein that is localized in the outer membrane of mitochondria (OMM). In addition to regulating mitochondrial gene expression as a nuclear TF, STAT6 in OMM inhibits mitochondrial fusion by blocking MFN2 dimerization. This implies that STAT6 has dual role in overall mitochondrial process. Moreover, mitochondrial accumulation of STAT6 in response to these findings reveal that STAT6 is a new regulator of mitochondrial processes including mitochondrial biogenesis and fusion/fission mechanisms.

2024-04-01 | GSE255693 | GEO

Mito-protective autophagy is impaired in erythroid cells of aged mtDNA-mutator mice

Project description:Somatic mitochondrial DNA (mtDNA) mutations contribute to the pathogenesis of age-related disorders, including myelodysplastic syndromes (MDS). The accumulation of mitochondria harboring mtDNA mutations in patients with these disorders suggests a failure of normal mitochondrial quality-control systems. The mtDNA-mutator mice acquire somatic mtDNA mutations via a targeted defect in the proofreading function of the mtDNA polymerase, PolgA, and develop macrocyticanemia similar to that of patients with MDS. We observed an unexpected defect in clearance of dysfunctional mitochondria at specific stages during erythroid maturation in hematopoietic cells from aged mtDNA-mutator mice. Mechanistically, aberrant activation of mechanistic target of rapamycin signaling and phosphorylation of uncoordinated 51-like kinase (ULK) 1 in mtDNA-mutator mice resulted in proteasome mediated degradation of ULK1 and inhibition of autophagy in erythroid cells. To directly evaluate the consequence of inhibiting autophagy on mitochondrial function in erythroid cells harboring mtDNA mutations in vivo, we deleted Atg7 from erythroid progenitors of wildtype and mtDNA-mutator mice. Genetic disruption of autophagy did not cause anemia in wild-type mice but accelerated the decline in mitochondrial respiration and development of macrocytic anemia in mtDNA-mutator mice. These findings highlight a pathological feedback loop that explains how dysfunctional mitochondria can escape autophagy-mediated degradation and propagate in cells predisposed to somatic mtDNA mutations, leading to disease. We used microarrays to identify expression profiles and pathways that are differentially activated or suppressed in Ter119+ bone marrow cells isolated from phlebotomized wildtype or Polg mutant mice

2015-04-21 | E-GEOD-57761 | biostudies-arrayexpress

Functional RNA dynamics are progressively governed by RNA destabilization during the adaptation to chronic hypoxia

Project description:Previous studies towards reduced oxygen availability mostly focused on changes in total mRNA expression neglecting underlying transcriptional and post-transcriptional events. Therefore, we generated a comprehensive overview of hypoxia-induced changes in total mRNA expression, global de novo transcription, and mRNA stability in monocytic THP-1 cells. Since hypoxic epi-sodes often persist for prolonged periods, we further compared adaptations to acute and chronic hypoxia. While total mRNA changes correlated well with enhanced transcription during short term hypoxia, mRNA destabilization gained importance under chronic conditions. Reduced mRNA stability not only added to compensatory attenuation of immune responses, but most no-tably to the reduction of nuclear-encoded mRNAs associated with various mitochondrial func-tions. These changes may prevent the futile production of new mitochondria under conditions where mitochondria cannot exert their full metabolic function and are indeed actively removed by mitophagy. The post-transcriptional mode of regulation might further allow for rapid recov-ery of mitochondrial capacities upon reoxygenation. Our results provide a comprehensive re-source of functional mRNA expression dynamics and underlying transcriptional and post-transcriptional regulatory principles during the adaptation to hypoxia. Furthermore, we specifically uncover mitochondrial functions controlled by RNA stability regulation in the con-text of hypoxia.

2022-06-01 | GSE199947 | GEO

Role of bcatenin in hepatocellular carcinoma

Project description:Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide. β-catenin is widely thought to be a major oncogene in HCC based on the frequency of mutations associated with aberrant Wnt signaling in HCC patients. Challenging this model, our data reveal that β-catenin nuclear accumulation is restricted to the late stage of the disease. Until then, β-catenin is primarily located at the plasma membrane in complex with multiple cadherin family members where it drives tumor cell survival by enhancing the signaling of growth factor receptors such as EGFR. Therefore, our study reveals the evolving nature of β-catenin in HCC to establish it as a compound tumor promoter during the progression of the disease.

2019-03-29 | PXD013095 | Pride

MITOCHONDRIAL Akt REGULATION OF HYPOXIC METABOLIC REPROGRAMMING

Project description:Hypoxia is a driver of aggressive tumor behavior, but the mechanisms are not completely understood. In a global phosphoproteomics screen, we now demonstrate that hypoxia induces the recruitment of Akt2 to tumor mitochondria, and Akt phosphorylation of pyruvate dehydrogenase kinase (PDK1) on Thr346. In turn, Akt-phosphorylated PDK1 shuts off oxidative phosphorylation via phosphorylation of the pyruvate dehydrogenase complex, and reprograms tumor metabolism towards glycolysis. Akt-phosphorylation of PDK1 is required to prevent autophagy, maintain cell viability and support tumor cell proliferation in hypoxia, in vivo. Therefore, mitochondrial Akt is a pathophysiologic switch for tumor adaptation in hypoxia.

2016-04-20 | MSV000079671 | MassIVE

Mitochondrial retrograde signaling in mammals is mediated by the transcriptional cofactor GPS2 via direct mitochondria-to-nucleus translocation [ChIP-seq]

Project description:As most of the mitochondrial proteome is encoded in the nucleus, mitochondrial functions critically depend on nuclear gene expression and bidirectional mito-nuclear communication. However, mitochondria-to-nucleus communication pathways are incompletely understood. Here, we identify G-Protein Pathway Suppressor 2 (GPS2) as a mediator of mitochondrial retrograde signaling and a key transcriptional activator of nuclear-encoded mitochondrial genes in mammals. GPS2 regulated translocation from mitochondria to nucleus is essential for the transcriptional activation of the nuclear stress response to mitochondrial depolarization and for supporting basal mitochondrial biogenesis in differentiating adipocytes and in brown adipose tissue from mice. In the nucleus, GPS2 recruitment to target gene promoters regulates histone H3K9 demethylation and RNA Polymerase II (POL2) activation through inhibition of Ubc13-mediated ubiquitination. These findings, together, reveal an unexpected layer of regulation of mitochondrial gene transcription, uncover a novel direct mitochondria-nuclear communication pathway and indicate that GPS2 retrograde signaling is a key component of the mitochondrial stress response in mammals.

2018-03-21 | GSE80992 | GEO

Mitochondrial retrograde signaling in mammals is mediated by the transcriptional cofactor GPS2 via direct mitochondria-to-nucleus translocation [GRO-seq]

2018-03-21 | GSE80990 | GEO

Mitochondrial retrograde signaling in mammals is mediated by the transcriptional cofactor GPS2 via direct mitochondria-to-nucleus translocation

2018-03-21 | GSE80994 | GEO

Mitochondrial retrograde signaling in mammals is mediated by the transcriptional cofactor GPS2 via direct mitochondria-to-nucleus translocation [RNA-seq]

2018-03-21 | GSE80993 | GEO

Single-cell transcriptomic analysis of two models of zebrafish beta-catenin-driven HCC

Project description:Up to 41% of hepatocellular carcinomas (HCCs) result from activating mutations in the CTNNB1 gene encoding β-catenin. β-catenin has dual cellular functions as a component of the Wnt signaling pathway and adherens junctions. HCC-associated CTNNB1 mutations stabilize the β-catenin protein, leading to nuclear and/or cytoplasmic localization of β-catenin and downstream activation of Wnt target genes. In patient HCC samples, β-catenin nuclear and cytoplasmic localization are typically patchy, even among HCC with highly active CTNNB1 mutations. The functional and clinical relevance of this heterogeneity in β-catenin activation are not well understood. To define mechanisms of β-catenin-driven HCC initiation, we generated a Cre-lox system that enabled switching on activated β-catenin in 1) a small number of hepatocytes in early development; or 2) the majority of hepatocytes in later development or adulthood. We discovered that switching on activated β-catenin in a subset of larval hepatocytes was sufficient to drive HCC initiation. To determine the role of Wnt/β-catenin signaling heterogeneity later in hepatocarcinogenesis, we performed RNA-seq analysis of zebrafish β-catenin-driven HCC. Ingenuity Pathway Analysis of differentially expressed genes in the Cre-lox HCC model revealed that “Cancer” and “Liver Tumor” categories were significantly altered, indicating transcriptional similarities with human HCC and other vertebrate HCC models. At the single-cell level, 2.9% to 15.2% of hepatocytes from zebrafish β-catenin-driven HCC expressed two or more of the Wnt target genes axin2, mtor, glula, myca, and wif1, indicating focal activation of Wnt signaling in established tumors. Thus, heterogeneous β-catenin activation drives HCC initiation and persists throughout hepatocarcinogenesis.

2019-09-27 | GSE137784 | 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