Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

YTHDC1 affects the ubiquitination level of RAD51 by negatively regulating UBE3A expression and inhibits colorectal cancer cells apoptosis

ABSTRACT: Understanding the role of YTHDC1 in colorectal cancer development and DNA damage repair is crucial for advancing treatment strategies. In our study, we found that YTHDC1 is expressed at significantly higher levels in high-malignancy tissues compared to low-malignancy tissues. Silencing YTHDC1 effectively inhibits the proliferation of colorectal cancer cell lines and significantly increases cell apoptosis. We identified RAD51 as a key downstream target of YTHDC1. Knockdown of YTHDC1 reduced RAD51 protein levels, while silencing RAD51 also inhibited cancer cell proliferation. Interestingly, RNA sequencing indicated that YTHDC1 deletion did not affect RAD51 transcription but increased its ubiquitination through WB experiment. Our analysis revealed that reducing YTHDC1 raised E3 ligase UBE3A levels, which is involved in RAD51 ubiquitination and ubiquitination experiments confirmed that RAD51 is one of the ubiquitination substrates of UBE3A. Co-immunoprecipitation experiments confirmed interactions among YTHDC1, UBE3A, and RAD51, suggesting they form a complex that regulates homologous repair processes. Our study provides new insights into how YTHDC1 modulates RAD51 ubiquitin levels through post-translational modifications, offering valuable information for developing effective colorectal cancer therapies.

ORGANISM(S): Homo sapiens

PROVIDER: GSE245860 | GEO | 2024/12/06

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

YTHDC1 affects the ubiquitination level of RAD51 by negatively regulating UBE3A expression and inhibits colorectal cancer cells apoptosis

Project description:YTHDC1 affects the ubiquitination level of RAD51 by negatively regulating UBE3A expression and inhibits colorectal cancer cells apoptosis

| PRJNA1030288 | ENA

Excessive UBE3A dosage impairs fine-tuning of retinoid acid signaling in autism spectrum disorders

Project description:The autism spectrum disorders (ASD) are a collection of disorders with heterogeneous etiology, exhibiting common traits including impaired social interactions and communications, repetitive behaviors. 15q11-q13 copy number variations (CNV) were found in 1-3% of ASD cases; of which the detailed mechanism of the major contributor UBE3A gene acted still remained elusive. Here we identified a key enzyme in RA synthesis, negatively regulated in ubiquitination-dependent mode promoted by UBE3A. Our data provide evidences linking UBE3A hyperactivity with ASD phenotypes, with implications for understanding ASD etiology and providing potential interventions in ASD clinical therapy.

2017-12-28 | GSE93207 | GEO

RAD51 knockout in murine liver (4-week)

Project description:RAD51 is a highly conserved DNA repair protein and is indispensable for the execution of homologous recombination, thereby participating in maintaining genomic stability. Since constitutive Rad51 knockout mice exhibit embryonic lethality, the physiological functions of RAD51, and the consequences of lacking it, are largely unknown. We herein demonstrated a critical role of RAD51 in postnatal liver development and regeneration. RAD51 is highly expressed during liver development and during regeneration following hepatectomy and hepatic injury, and is also elevated in liver-related diseases. We generated hepatocyte-specific Rad51 deletion mouse model (Rad51-CKO) to evaluate the function of RAD51 in liver development and regeneration.RAD51 deletion in postnatal hepatocytes results in aborted mitosis, global polyploidization, oxidative stress and cellular senescence. Remarkable liver fibrosis occurs as early as in 3-month-old Rad51fl/fl; Alb-Cre+/+ mice.The senescence-associated secretory phenotype in the livers of Rad51-CKO mice creates a niche that favors the activation and propagation of hepatic progenitor cells (HPCs) in which Rad51 is spared due to lack of Alb-Cre expression. The Rad51 functional HPCs and immature hepatocytes can thus proliferate vigorously, acquire increased malignancy, and eventually give rise to HCC. Our results thus demonstrate a novel function of RAD51 in liver development, homeostasis and tumorigenesis. The RAD51-CKO mice represent a unique genetic model for premature liver senescence, fibrosis, impaired regeneration and hepatocellular carcinogenesis.

2025-01-22 | GSE243614 | GEO

RAD51 knockout in murine liver (11-week)

2025-01-22 | GSE243719 | GEO

UBE3A-mediated regulation of imprinted genes and epigenome-wide marks in human neurons

Project description:The dysregulation of genes in neurodevelopmental disorders that lead to social and cognitive phenotypes is a complex, multilayered process involving both genetics and epigenetics. Parent-of-origin effects of deletion and duplication of the 15q11-q13 locus leading to Angelman, Prader-Willi, and Dup15q syndromes are due to imprinted genes, including UBE3A, which is maternally expressed exclusively in neurons. UBE3A encodes a ubiquitin E3 ligase protein with multiple downstream targets, including RING1B, which in turn monoubiquitinates histone variant H2A.Z. To understand the impact of neuronal UBE3A levels on epigenome-wide marks of DNA methylation, histone variant H2A.Z positioning, active H3K4me3 promoter marks, and gene expression, we took a multi-layered genomics approach. We performed an siRNA knockdown of UBE3A in two human neuroblastoma cell lines, including parental SH-SY5Y and the SH(15M) model of Dup15q. Genes differentially methylated across cells with differing UBE3A levels were enriched for functions in gene regulation, DNA binding, and brain morphology. Importantly, we found that altering UBE3A levels had a profound epigenetic effect on the methylation levels of up to half of known imprinted genes. Genes with differential H2A.Z peaks in SH(15M) compared to SH-SY5Y were enriched for ubiquitin and protease functions and associated with autism, hypoactivity, and energy expenditure. Together, these results support a genome-wide epigenetic consequence of altered UBE3A levels in neurons and suggest that UBE3A regulates an imprinted gene network involving DNA methylation patterning and H2A.Z deposition.

2017-09-26 | GSE103309 | GEO

Ube3a-ATS characterization with strand-speicific microarray

Project description:This strand-specific array is performed to characterize expression features of Ube3a-ATS, including its imprinting status, its exon-intron structure, its transcriptional initiation and termination site as well as its polyadenylation status. The array contains reverse-complementary probes detecting transcripts from both strands and therefore we are able to pick up signal from both Ube3a sense and antisense. By comparing wild-type with various mutants, and total RNA with polyA RNA, we concluded that Ube3a-ATS is a paternally imprinted gene covering the whole gene body of Ube3a in the antisense orientation. It does not have an obvious exon-intron structure. Its transcription initiates at Snrpn major promoter and terminates ~40kb upstream of Ube3a transcriptional start site. Total RNA from Snrpn-Ube3a maternal deletion mutant (del s-u/+), its wild-type littermate, paternal deletion mutant and its wildtype littermate were analyzed. Mutant mice with S-U maternal deletion and Snrpn promoter paternal deleiton which leads to depletion of Ube3a-ATS (del s-u/0.9 and del s-u/4.8) were also analyzed. polyA RNA was purified from the sample 2 and sample 4. All eight samples were hybridized to the custom 8X60k Agilent CGH array.

2012-05-02 | E-GEOD-29254 | biostudies-arrayexpress

The E3 Ubiquitin Ligase UBE3A Antagonizes Steatosis by Targeting the Pro-Steatotic Epigenetic Regulator MLL4 for Degradation

Project description:Regulation of the stability of epigenetic regulators offers unique opportunities for epigenetic therapies. However, this strategy has been poorly explored. Here we report that the E3 ubiquitin ligase UBE3A binds and ubiquitylates the histone H3-lysine 4-methyltransferase MLL4 (aka KMT2D) as a new substrate for degradation. Using Ube3a knockout and UBE3A-overexpressing transgenic mouse models, we show that, in the liver, UBE3A levels are inversely correlated with levels of MLL4, its functional surrogate marker H3-lysine 4-monomethylation, and expression of the recently identified steatosis target genes of MLL4. Consistently, Ube3a knockout mice are highly susceptible to high-fat diet-induced steatosis relative to their littermate control mice, and this phenotype is rescued by deletion of a copy of Mll4. Therefore, UBE3A indirectly exerts an epigenetic gene regulation activity through targeting MLL4 for degradation. Also this UBE3A-MLL4 axis presents a novel therapeutic venue for treating various MLL4-directed pathogeneses.

2019-03-18 | GSE103553 | GEO

Expression data from SKOV3.ip cells by knockdown RAD51-AS1 expression.

Project description:Long non-coding RNAs (lncRNA) have been shown to play crucial roles in tumorigenesis. Little is known about lncRNA RAD51-AS1 in diseases. Here, we investigated the role of RAD51-AS1 in Epithelial ovarian cancer. Silencing RAD51-AS1 inhibited proliferation through cell cycle arrest and promotion in apoptosis, both in vitro and in vivo. But the mechanism of RAD51-AS1 downstream regulation remains unclear. In order to identify the downstream regulation of RAD51-AS1 in epithelial ovarian cancer, we used antisene oligotides targeting RAD51-AS1 / negative control to transfect Skov3.ip cells. Then, we used microarrays to identified differential expression genes and to look for possible target genes by knockdown RAD51-AS1 expression.

2017-08-17 | GSE89374 | GEO

Ube3a-ATS characterization with strand-speicific microarray

2012-05-03 | GSE29254 | GEO

UBE3A Deficiency Downregulates Retinoic Acid Signalling Pathway

Project description:Ubiquitin-protein ligase E3A (UBE3A) has dual functions as a E3 ubiquitin-protein ligase and coactivator of nuclear hormone receptors. Mutations or deletions of the maternally inherited UBE3A gene cause Angelman syndrome. Here, we performed transcriptome profiling in the hippocampus of Ube3am+/p+ and Ube3am-/p+ mice, and determined that the expression of the retinoic acid (RA) signalling pathway was downregulated in Ube3a-deficient mice compared to WT mice. Furthermore, we demonstrated that UBE3A directly interacts with RARα and may function as a coactivator of the nuclear receptor RARα to participate in the regulation of gene expression. Loss of UBE3A expression caused the downregulation of the expression of RA-related genes, including Erbb4, Dpysl3, Calb1, Pten and Arhgap5 in Ube3am-/p+ mice brain tissues. This work revealed a new role for UBE3A in regulating retinoic acid (RA) signalling downstream genes and hopefully to shed light on the potential drug target of AS.

2021-03-15 | GSE168889 | 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