Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The CXXC5-CRL4B-NuRD Repressor Complex Promotes Breast Carcinogenesis by Regulating the TSC1/mTOR pathway

ABSTRACT: Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for CXXC5,CUL4B as well as MTA1 in MCF-7 cells.The pathophysiological function of the CXXC family-member CXXC5 remains to be explored. Here we report that CXXC5 is physically associated with the CRL4B complex and the NuRD complex. Genome-wide investigation of transcriptional targets revealed that the CXXC5/CRL4B/NuRD complex represses a panel of genes including TSC1 that are critically involved in cell growth and the regulation of the mTOR pathway, leading to activation of PD-L1. Intriguingly, CXXC5 expression was increased after stimulation with vitamin B2, whereas vitamin D treatment was accompanied by decreased expression of CXXC5. We demonstrated that the CXXC5-CRL4B-NuRD complex promotes cancer cell proliferation. Elevation of CXXC5, CUL4B, and MTA1 expression during cancer progression corresponded to diminished TSC1 expression, and high levels of CXXC5, CUL4B, and MTA1 strongly correlated with higher histological grades and poor prognosis. We further identified that CXXC5 is bimodally regulated by different kinds of vitamins. Our study revealed that CXXC5-mediated TSC1 suppression activates the mTOR pathway, reduces autophagic cell death, induces PD-L1-mediated immune suppression and results in tumor development, providing a possible mechanistic insight into the pathophysiological function of CXXC5.

ORGANISM(S): Homo sapiens

PROVIDER: GSE205362 | GEO | 2022/12/12

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

CUL4B ChIP-sequencing in non-treated MDA-MB-231 cells

Project description:Cullin 4B (CUL4B) is a scaffold protein of the CUL4B-Ring E3 ligase (CRL4B) complex. Here, we found that CRL4B interacted with transcriptional corepressor complexes. Our results supporting CUL4B as a potential target of cancer therapy.

2021-03-25 | GSE124611 | GEO

ChIP-on-chip from MDA-MB-231 cells with PHF1, CUL4B and PRMT5

Project description:It has been reported that PHF1, CUL4B and PRMT5 all play important roles in epigenetic regulation. We reported that PHF1, CRL4B and PRMT5 may act as a complex in transcriptional regulation and have a vital effect in breast cancer progression. So we performed ChIP-on-chip assays to find unique promoters co-targeted by PHF1, CUL4B and PRMT5. PHF1, CUL4B and PRMT5 have a predominant cooperation, at least in MDA-MB-231 cells. comparison of PHF1, CUL4B and PRMT5 target genes

2016-07-07 | E-GEOD-84071 | biostudies-arrayexpress

PRMT6 and PARP1 sequencing in non-treated MDA-MB-231 cells

Project description:Here, we examined the interactions between PRMT6, poly(ADP-ribose) polymerase 1 (PARP1), and the cullin 4 B (CUL4B)-Ring E3 ligase (CRL4B) complex, to form a transcription-repressive complex that co-occupies the core clock gene PER3 promoter.

2023-05-24 | GSE210947 | GEO

ChIP-on-chip from MDA-MB-231 cells with PHF1, CUL4B and PRMT5

2016-07-07 | GSE84071 | GEO

ChIP-on-chip from KYSE410 cells with CUL4B, EZH2 and BMI

Project description:A total of 619 unique promoters were found to be co-targeted by CUL4B and EZH2, among which only 53 were overlapped with the 891 targets of BMI EZH2/PRC2 and CUL4B/CRL4B have a predominant cooperation, at least in KYSE410 cells.

2012-10-17 | GSE41639 | GEO

Regulation of PERK-eIF2Î± Signaling by Tuberous Sclerosis Complex-1 Controls Homeostasis and Survival of Myelinating Oligodendrocytes

Project description:Tuberous sclerosis complex (TSC), an autosomal dominant disorder caused by mutations in either TSC1 or TSC2, exhibits white matter abnormalities including CNS myelin deficits. however, underlying mechanisms are not fully understood. Here we find that, unexpectedly, constitutive activation of mTOR signaling caused by Tsc1 deletion in the oligodendrocyte lineage results in severe myelination defects and oligodendrocyte cell death. Expression profiling analysis reveals that Tsc1 ablation induces prominent endoplasmic reticulum (ER) stress responses through the PERKâeIF2Î± dependent signaling axis and activates Fas-JNK apoptotic pathways. Our studies suggest that TSC1-mTOR signaling acts as an important checkpoint for maintaining oligodendrocyte homeostasis. Gene expression profiling of optic nerve from P12 control and Tsc1cKO mice

2016-07-22 | E-GEOD-74893 | biostudies-arrayexpress

RNAi profiling by array of Drosophila S2 cells with RNAi knock down of NURK subunits and TTK69 transcription factor

Project description:RNAi knockdown of NURD subunits: MI2/CG8103, MEP1/CG1244, MTA1-like/CG2244; and TTK69 transcription factor

2010-07-01 | E-TABM-1010 | biostudies-arrayexpress

MUC1-C ACTIVATES THE NURD COMPLEX IN DEDIFFERENTIATION OF TRIPLE-NEGATIVE BREASTCANCER CELLS

Project description:The NuRD chromatin remodeling and deacetylation complex, which includes MTA1, MBD3, CHD4 and HDAC1 among other components, is of importance for development and cancer progression. The oncogenic MUC1-C protein activates EZH2 and BMI1 in the epigenetic reprogramming of triple-negative breast cancer (TNBC) cells. However, there is no known link between MUC1-C and chromatin remodeling complexes. The present studies demonstrate that MUC1-C binds directly to the MYC HLH/LZ domain. In turn, we identified a previously unrecognized MUC1-C®MYC pathway that regulates the NuRD complex. We show that MUC1-C/MYC complexes selectively activate the MTA1 and MBD3 genes and posttranscriptionally induce CHD4 expression in basal- and not luminal-type BC cells. The results further show that MUC1-C forms complexes with these NuRD components on the ESR1 promoter. In this way, silencing MUC1-C (i) decreased MTA1/MBD3/CHD4/HDAC1 occupancy and increased H3K27 acetylation on the ESR1 promoter, and (ii) induced ESR1 expression and downstream estrogen response pathways. We also demonstrate that targeting MUC1-C and these NuRD components induces expression of FOXA1, GATA3 and other markers associated with the luminal phenotype. These findings and results from gain-of-function studies support a model in which MUC1-C activates the NuRD complex in driving luminal®basal dedifferentiation and plasticity of TNBC cells.

2020-03-05 | GSE134147 | GEO

MTA1 interacts with primary RNAs to regulate expression and AS by protein dependent manner [ChIP]

Project description:MTA1 is known as its metastatic and invasive function in cancers and the core member of NuRD complex. But the mechanism of regulating gene expression by MTA1 is limited. Besides the interaction with chromosome, MTA1 may play important role at the transcriptional level. We performed co- immunoprecipitation (co-IP) on HCT116 cells and found numerous RNA binding proteins (RBPs), which functions as spliceosome and RNA transport. We then validated that MTA1 interacts with RBPs by RNA dependent manner. By performing the CLIP-seq of MTA1, ten thousands of peaks and thousands of genes were emerged. More detailed analysis and high level of intronic peaks reveal MTA1 prefers to bind pre-mRNAs and regulate the alternative splicing progression by binding the splice site. High overlapping between MTA1 binding and MTA1 regulated genes highlights the direct regulation of RNAs by MTA1 coupling with RBPs. LTK is one of the obvious examples regulated by MTA1. Together, these findings uncover a novel mechanism of MTA1 regulation in transcriptional level as RBPs, and suggest MTA1 regulates pre-mRNA splicing with other RBPs.

2021-01-04 | GSE102632 | GEO

MTA1 interacts with primary RNAs to regulate expression and AS by protein dependent manner [RNA]

2021-01-04 | GSE102635 | 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