Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The deubiquitinase USP1 promotes the progression of AML by stabilizing ID1 [RNAseq_AML_shUSP1]

ABSTRACT: Acute myeloid leukemia (AML) represents a clonal malignant disorder affecting the hematopoietic system, predominantly featuring abnormal clonal proliferation of myeloid precursor cells and linked to unfavorable prognosis. This investigation seeks to improve clinical outcomes through examing the mechanistic role ubiquitin-specific protease 1 (USP1) in AML. Data analysis from The Cancer Genome Atlas (TCGA) and TARGET databases demonstrated that USP1 exhibits high expression in AML, where increased show positive correlation with poor prognostic outcomes. In vitro studies using short hairpin RNA (shRNA) for USP1 knockdown showed significant suppression of AML cell proliferation and enhanced apoptosis. Additionally, in vivo investigations indicated that USP1 knockdown inhibited tumor growth and enhanced survival rates. The USP1 inhibitor SJB3-019A displayed similar effects on AML cells. Co-immunoprecipitation (CO-IP) coupled with mass spectrometry analysis indicated that USP1 associates with ID1, mediating its function via deubiquitination mechanisms. CUT&Tag findings additionally demonstrated that ID1 modulates target genes involved in AML. This investigation confirms that USP1 serves a critical role in facilitating the proliferation and survival of AML cells through ID1 stabilization. The findings suggest that the USP1 inhibitor SJB3-019A represents a promising new therapeutic approach for treating AML.

ORGANISM(S): Homo sapiens

PROVIDER: GSE312505 | GEO | 2026/04/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

The deubiquitinase USP1 promotes the progression of AML by stabilizing ID1 [ID1 CUT&Tag in AML]

Project description:Acute myeloid leukemia (AML) represents a clonal malignant disorder affecting the hematopoietic system, predominantly featuring abnormal clonal proliferation of myeloid precursor cells and linked to unfavorable prognosis. This investigation seeks to improve clinical outcomes through examing the mechanistic role ubiquitin-specific protease 1 (USP1) in AML. Data analysis from The Cancer Genome Atlas (TCGA) and TARGET databases demonstrated that USP1 exhibits high expression in AML, where increased show positive correlation with poor prognostic outcomes. In vitro studies using short hairpin RNA (shRNA) for USP1 knockdown showed significant suppression of AML cell proliferation and enhanced apoptosis. Additionally, in vivo investigations indicated that USP1 knockdown inhibited tumor growth and enhanced survival rates. The USP1 inhibitor SJB3-019A displayed similar effects on AML cells. Co-immunoprecipitation (CO-IP) coupled with mass spectrometry analysis indicated that USP1 associates with ID1, mediating its function via deubiquitination mechanisms. CUT&Tag findings additionally demonstrated that ID1 modulates target genes involved in AML. This investigation confirms that USP1 serves a critical role in facilitating the proliferation and survival of AML cells through ID1 stabilization. The findings suggest that the USP1 inhibitor SJB3-019A represents a promising new therapeutic approach for treating AML.

2026-04-01 | GSE312506 | GEO

The deubiquitinase USP1 promotes the progression of AML by stabilizing ID1 [ID1 CUT&Tag in AML]

Project description:The deubiquitinase USP1 promotes the progression of AML by stabilizing ID1 [ID1 CUT&Tag in AML]

| PRJNA1374084 | ENA

NeuroD1-USP1-N-Myc axis drives tumor progression in neuroblastoma [ATAC-seq]

Project description:Neuroblastoma, derived from the sympathetic neural crest, represents the most prevalent extracranial solid tumor in children. Amplification of MYCN is widely recognized as a key indicator of unfavorable prognosis in neuroblastoma. However, the structural properties of the N-Myc protein encoded by MYCN have hindered the development of direct inhibitors with favorable drug-like properties. Therefore, uncovering the upstream regulatory mechanisms of N-Myc offers promising new targets for therapeutic intervention in MYCN-amplified neuroblastoma. In this study, we identified NeuroD1 as a critical regulator closely associated with MYCN amplification. NeuroD1 was shown to drive the proliferation of MYCN-amplified neuroblastoma cells both in vitro and in vivo. Mechanistically, NeuroD1 knockdown led to increased K48-linked polyubiquitination of N-Myc, resulting in its proteasomal degradation. Through transcriptional target screening, USP1 was identified as a key downstream effector of NeuroD1. Further investigation revealed that USP1 interacts with N-Myc, removing K48-linked polyubiquitin chains and stabilizing the protein. Importantly, Pimozide, an FDA-approved USP1 inhibitor, was found to effectively suppress USP1 expression, reduce N-Myc levels, and inhibit neuroblastoma cell proliferation. These findings highlight a novel oncogenic axis in MYCN-amplified neuroblastoma, where NeuroD1 transcriptionally upregulates USP1, facilitating N-Myc stabilization and tumor progression. Additionally, our results underscore the therapeutic potential of repurposing Pimozide as a viable treatment strategy for this aggressive tumor subtype.

2025-05-01 | GSE285630 | GEO

NeuroD1-USP1-N-Myc axis drives tumor progression in neuroblastoma [ChiP-seq]

2025-05-01 | GSE285629 | GEO

NeuroD1-USP1-N-Myc axis drives tumor progression in neuroblastoma [CUT&TAG]

2025-05-01 | GSE285628 | GEO

NeuroD1-USP1-N-Myc axis drives tumor progression in neuroblastoma [RNA-seq]

2025-05-01 | GSE285627 | GEO

The deubiquitinase USP1 promotes the progression of AML by stabilizing ID1 [RNAseq_AML_shUSP1]

Project description:The deubiquitinase USP1 promotes the progression of AML by stabilizing ID1 [RNAseq_AML_shUSP1]

| PRJNA1374079 | ENA

Ubiquitinated PCNA drives USP1 synthetic lethality in cancer

Project description:CRISPR Cas9-based functional genomics screening is a powerful approach for identifying and characterizing novel oncology drug targets. Here, we elucidate the synthetic lethal mechanism of deubiquitinating enzyme USP1 in cancers with underlying DNA damage vulnerabilities, specifically BRCA1/2 mutant tumors and a subset of BRCA1/2 wild-type (WT) tumors. In sensitive cells, pharmacological inhibition of USP1 leads to decreased DNA synthesis concomitant with the induction of S-phase-specific DNA damage. Genome-wide CRISPR-Cas9 screens identified RAD18 and UBE2K, which promote PCNA mono- and polyubiquitination respectively, as downstream mediators of USP1 dependency. The accumulation of mono- and polyubiquitinated PCNA following USP1 inhibition was associated with a reduction in total PCNA protein levels. Ectopic expression of WT and ubiquitin-dead K164R PCNA reversed USP1 inhibitor sensitivity. Our results demonstrate, for the first time, that USP1 dependency hinges on the aberrant processing of mono- and polyubiquitinated PCNA. Moreover, this mechanism of USP1 dependency extends beyond BRCA1/2 mutant tumors to a novel subset of BRCA1/2 WT cancer enriched in ovarian and lung lineages. We further show PARP and USP1 inhibition are strongly synergistic in BRCA1/2 mutant cell lines and xenograft models. We postulate USP1 dependency unveils a previously uncharacterized vulnerability linked to post-translational modifications of PCNA. Taken together, USP1 inhibition may represent a unique therapeutic strategy for BRCA1/2 mutant tumors and a subset of BRCA1/2 WT tumors.

2022-09-27 | GSE214121 | GEO

Gene expression changes in breast cancer cells upon USP1 knockdown [RNA-Seq]

Project description:To explore the function of deubiquitinase USP1 in breast cancer cells, we performed RNA sequencing to analyze the expression pattern changes by knockdown of USP1 in MCF7 cells.

2021-03-14 | GSE111838 | GEO

USP1 modulates hepatocellular carcinoma progression via Hippo/TAZ axis

Project description:To investigate the function of USP1 in the HCC.

2022-11-23 | GSE218366 | GEO