Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Molecular Signatures of CB-6644 inhibition of the RUVBL1/2 complex in Multiple Myeloma [RNA-seq]

ABSTRACT: Multiple Myeloma is the second most hematological cancer. RUVBL1 and RUVBL2 forms a subcomplex of many chromatin remodeling complexes implicated in cancer progress. As an inhibitor specific to the RUVBL1/2 complex, CB-6644 exhibits remarkable anti-tumor activity in xenograft models of Burkitt’s lymphoma and multiple myeloma (MM). In this work, we defined transcriptional signatures corresponding to CB-6644 treatment in MM cells and determined underlying epigenetic changes in terms of chromatin accessibility.CB-6644 upregulated biological processes related to interferon response and downregulated those linked to cell proliferation in MM cells. Transcriptional regulator inference identified ATF4/CEBP and E2Fs as regulators for downregulated genes and MED1 and MYC as regulators for upregulated genes. CB-6644-induced changes in chromatin accessibility occurred mostly in non-promoter regions. Footprinting analysis identified transcription factors implied in modulating chromatin accessibility in response to CB-6644 treatment, including ATF4/CEBP and IRF4. Lastly, integrative analysis of transcription responses to various chemical compounds of the molecular signature genes from public gene expression data identified CB-5083, a p97 inhibitor, as a synergistic candidate with CB66-44 in MM cells, but experimental validation refuted this hypothesis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE271840 | GEO | 2024/08/19

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Molecular Signatures of CB-6644 inhibition of the RUVBL1/2 complex in Multiple Myeloma [ATAC-seq]

Project description:Multiple Myeloma is the second most hematological cancer. RUVBL1 and RUVBL2 forms a subcomplex of many chromatin remodeling complexes implicated in cancer progress. As an inhibitor specific to the RUVBL1/2 complex, CB-6644 exhibits remarkable anti-tumor activity in xenograft models of Burkitt’s lymphoma and multiple myeloma (MM). In this work, we defined transcriptional signatures corresponding to CB-6644 treatment in MM cells and determined underlying epigenetic changes in terms of chromatin accessibility.CB-6644 upregulated biological processes related to interferon response and downregulated those linked to cell proliferation in MM cells. Transcriptional regulator inference identified ATF4/CEBP and E2Fs as regulators for downregulated genes and MED1 and MYC as regulators for upregulated genes. CB-6644-induced changes in chromatin accessibility occurred mostly in non-promoter regions. Footprinting analysis identified transcription factors implied in modulating chromatin accessibility in response to CB-6644 treatment, including ATF4/CEBP and IRF4. Lastly, integrative analysis of transcription responses to various chemical compounds of the molecular signature genes from public gene expression data identified CB-5083, a p97 inhibitor, as a synergistic candidate with CB66-44 in MM cells, but experimental validation refuted this hypothesis.

2024-08-19 | GSE271838 | GEO

Gene expression profile of multiple myeloma cell lines treated with CB-5083

Project description:The goal was to determine the gene expression differences between CB-5083 and Bortezomib treated multiple myeloma cell lines Inhibition of the AAA ATPase, p97, was recently shown to be a novel method for targeting the ubiquitin proteasome system (UPS) and CB-5083, a first in class inhibitor of p97, has demonstrated broad antitumor activity in a range of both hematological and solid tumor models. Here, we show that CB-5083 has robust activity against multiple myeloma (MM) cell lines and a number of in vivo MM models. Treatment with CB-5083 is associated with accumulation of ubiquitinated proteins, induction of the unfolded protein response (UPR) and apoptosis. CB-5083 decreases viability in MM cell lines and patient derived MM cells, including those with background proteasome inhibitor (PI) resistance. CB-5083 has a unique mechanism of action that combines well with PIs which is likely owing to the p97-dependent retro-translocation of the transcription factor, Nrf1, which transcribes proteasome subunit genes following exposure to a PI. In vivo studies using clinically relevant MM models demonstrate that single-agent CB-5083 inhibits tumor growth and combines well with MM standard of care agents. Our preclinical data demonstrate the efficacy of CB-5083 in several MM disease models and provide the rationale for clinical evaluation as monotherapy and in combination in MM.

2017-10-26 | GSE101923 | GEO

RUVBL1 and RUVBL2 as novel druggable DNA Damage Response regulators in the MYCN regulatory network in neuroblastoma

Project description:To understand its role RUVBL1/2 in neuroblastoma, we inhibited RUVBL1/2 ATPase activity two independent cell lines, SK-N-AS and CBL-BA, with 250 nM CB-6644 at 0, 24, 48, and 72 hrs and performed RNA sequencing.

2024-08-31 | E-MTAB-13137 | biostudies-arrayexpress

Effect of inhibition of VCP on gene expression during colorectal cancer progression of HCT116 cells

Project description:To investigate the signaling patheway of VCP regulation PD-L1 in colorectal cancer cells, HCT116 cells were treated with CB-5083. We then performed gene expression profiling analysis using data obtained from RNA-seq of 3 different cells CB-5083 treatment and untreatment.

2023-10-18 | GSE201778 | GEO

HCT116 cells treated with the p97 inhibitior CB-5083

Project description:The goal of this study was to analyze differential gene expression 8 hr after treatment of CB-5083, a small molecule inhibitor of p97 (VCP), in HCT116 cells grown in culture. DMSO treated cells were compared to cells treated with 1uM CB-5083 after 8 hr.

2015-11-09 | E-GEOD-73588 | biostudies-arrayexpress

RNA-seq of human ovarian cancer cell line OVSAHO parental and CB-5083-resistant cells

Project description:The goal of this experiment is to identify differentially expressed genes between parental OVSAHO cells and CB-5083-resistant OVSAHO cells. Each group is treated with 5 microM CB-5083 for 6 hours and total RNA was extracted with Trizol. RNA sequencing library was performed using Illumina RNA library kit.

2018-11-02 | E-MTAB-7328 | biostudies-arrayexpress

RUVBL1/RUVBL2 ATPase Activity Drives PAQosome Maturation, DNA Replication and Radioresistance in Lung Cancer

Project description:RUVBL1 and RUVBL2 (collectively RUVBL1/2) are essential AAA+ ATPases that function as co-chaperones and have been implicated in cancer. Here we investigated the molecular and phenotypic role of RUVBL1/2 ATPase activity in non-small cell lung cancer (NSCLC). We find that RUVBL1/2 are overexpressed in NSCLC patient tumors, with high expression prognostic of poor survival. Utilizing a highly specific inhibitor of RUVBL1/2 ATPase activity, we show that RUVBL1/2 ATPase activity is necessary for the maturation of the PAQosome, a large RUVBL1/2-dependent multiprotein complex. We also show that RUVBL1/2 have roles in DNA replication, as inhibition of their ATPase activity impedes RPA loading at replication forks, decreases fork stability, and ultimately results in replication catastrophe and cancer cell death. While in vivo pharmacological inhibition of RUVBL1/2 results in modest antitumor activity, it synergizes with radiation in NSCLC, but not normal cells, an attractive property for future preclinical development.

2019-12-18 | GSE107637 | GEO

RNA-seq and MYC ChIP-seq in A673 Ewing sarcoma cells with RUVBL1 knockout

Project description:This dataset examined the effect of RUVBL1 knockout in A673 Ewing sarcoma cells. The gene expression profiling (RNA-seq) and the chromatin targeting of MYC (ChIP-seq) are reported.

2023-03-27 | GSE182378 | GEO

Homo sapiens

Project description:Gene expression profile of multiple myeloma cell lines treated with CB-5083

| PRJNA395929 | ENA

HCT116 cells treated with the p97 inhibitior CB-5083

Project description:The goal of this study was to analyze differential gene expression 8 hr after treatment of CB-5083, a small molecule inhibitor of p97 (VCP), in HCT116 cells grown in culture.

2015-11-09 | GSE73588 | 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