Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

BET Protein Inhibitor JQ1 Induces Cell Cycle Arrest in Mesenchymal Stem Cells

ABSTRACT: Efficacy and safety of anticancer drugs are traditionally studied using cancer cell lines and animal models. Recently, a potential anticancer agent, JQ1, an inhibitor of bromodomain and extra terminal (BET) protein, has been shown to promote apoptosis of cancerous cells by arresting them in G1 phase of the cell cycle. However, the effect of JQ1 on normal cells is poorly understood. In this study, we investigated the safety of JQ1 by using human umbilical cord mesenchymal stem cells (MSCs) as an in vitro model system. Our results indicated that JQ1 induced cell cycle arrest in G1 phase of MSCs, but did not promote apoptosis. Microarray analysis of MSCs treated with JQ1 indicated that it down-regulated genes involved not only in cell cycle regulation but also DNA replication, mitosis, and cell division. Although many studies have suggested the potential of JQ1 as an anticancer agent, our findings suggest that it caused a deleterious effect on normal cells and may not be safe for anticancer therapy.

ORGANISM(S): Homo sapiens

PROVIDER: GSE70577 | GEO | 2016/02/12

SECONDARY ACCESSION(S): PRJNA289064

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

BET Protein Inhibitor JQ1 Induces Cell Cycle Arrest in Mesenchymal Stem Cells

Project description:Efficacy and safety of anticancer drugs are traditionally studied using cancer cell lines and animal models. Recently, a potential anticancer agent, JQ1, an inhibitor of bromodomain and extra terminal (BET) protein, has been shown to promote apoptosis of cancerous cells by arresting them in G1 phase of the cell cycle. However, the effect of JQ1 on normal cells is poorly understood. In this study, we investigated the safety of JQ1 by using human umbilical cord mesenchymal stem cells (MSCs) as an in vitro model system. Our results indicated that JQ1 induced cell cycle arrest in G1 phase of MSCs, but did not promote apoptosis. Microarray analysis of MSCs treated with JQ1 indicated that it down-regulated genes involved not only in cell cycle regulation but also DNA replication, mitosis, and cell division. Although many studies have suggested the potential of JQ1 as an anticancer agent, our findings suggest that it caused a deleterious effect on normal cells and may not be safe for anticancer therapy. Human umbilical cord derived MSCs were cultured in vitro and treated with either 100 nM or 500 nM JQ1 for 24 hrs. Gene expression of treated cells was compared to untreated cultured cells.

2016-02-12 | E-GEOD-70577 | biostudies-arrayexpress

Expression data from Adriamycin-treated Emu-myc; Suv39h1-/- B-cell lymphoma

Project description:Oncogene-induced senescence (OIS), a terminal cell cycle block countering (pre)neoplastic lesions, is characterised on the molecular level by trimethylated histone H3 lysine 9 (h3K9me3), a transcriptionally repressive chromatin mark linked to silencing of S-phase-promoting genes. Whether H3K9-governed chromatin remodelling influences anticancer treatment-induced senescence (TIS) and whether functional control of this mark impacts on treatment outcome is not known. We used global gene expression profiling by microarrays to gain insight into the molecular responses of Emu-myc; Suv39h1-/- B-cell lymphoma cells to senescence-inducing anticancer agent Adriamycin (ADR).

2013-07-04 | GSE44355 | GEO

Time course of oxidative stress responses in yeast, caused by Menadione or hydrogen peroxide

Project description:Oxidative stress caused by Menadione or Hydrogen peroxide in synchronized Saccharomyces cerevisiae cultures. Alpha factor synchronized cultures (0.2-0.4 OD), treated at the beginning of S phase (25 min after release from G1 arrest) with either 2 mM Menadione (MD) or 0.24 mM Hydrogen peroxide (HP), show cell cycle effects. Cells treated with MD arrested at G1. Cells treated with HP delayed at S and then, after removal of HP at 135 minutes , continued the cell cycle, only to arrest at G2/M. Growth was carried out in 30C with shaking (295 rpm). Two time course experiments were performed with each oxidative stress agent, designated as H2O2 and H2O2_II, MD and MD_II. Keywords = oxidative stress Keywords = menadione Keywords = hydrogen peroxide Keywords = time course Keywords = cell cycle Keywords = yeast

2005-02-04 | E-GEOD-2239 | biostudies-arrayexpress

Time course of oxidative stress responses in yeast, caused by Menadione or hydrogen peroxide

2005-02-04 | GSE2239 | GEO

Re-configuration of Chromatin Structure During the Mitosis-G1 Phase Progression

Project description:Chromatin architecture is temporarily disrupted during mitosis. Yet, how chromatin architecture is reconfigured during M-G1 phase transition is unknown. To examine this, we performed Hi-C experiments on cell populations at defined cell cycle stages between mitosis and G1 phase.

2019-11-27 | GSE129997 | GEO

Unscheduled DNA replication in G1 causes genome instability and damage signatures indicative of replication collisions [mRNA-seq]

Project description:DNA replicates once per cell cycle. Interfering with the regulation of DNA replication initiation generates genome instability through over-replication and has been linked to early stages of cancer development. Here, we engineered genetic systems in budding yeast to induce unscheduled replication in the G1-phase of the cell cycle. Unscheduled G1 replication initiated at canonical S-phase origins. We quantified the composition of replisomes in G1- and S-phase and identified firing factors, polymerase alpha, and histone supply as factors that limit replication outside S-phase. G1 replication per se did not trigger cellular checkpoints. Subsequent replication during S-phase, however, resulted in over-replication and led to chromosome breaks and chromosome-wide, strand-biased occurrence of RPA-bound single-stranded DNA indicating head-to-tail replication collisions as a key mechanism generating genome instability upon G1 replication. Low-level, sporadic induction of G1 replication induced an identical response, indicating findings from synthetic systems are applicable to naturally occurring scenarios of unscheduled replication initiation.

2022-11-08 | GSE208589 | GEO

Unscheduled DNA replication in G1 causes genome instability and damage signatures indicative of replication collisions [ChIP-seq]

Project description:DNA replicates once per cell cycle. Interfering with the regulation of DNA replication initiation generates genome instability through over-replication and has been linked to early stages of cancer development. Here, we engineered genetic systems in budding yeast to induce unscheduled replication in the G1-phase of the cell cycle. Unscheduled G1 replication initiated at canonical S-phase origins across the genome. We quantified differences in replisomes in G1- and S-phase and identified firing factors, polymerase α, and histone supply as factors that limit replication outside S-phase. G1 replication per se did not trigger cellular checkpoints. Subsequent replication during S-phase, however, resulted in over-replication and led to chromosome breaks via head-to-tail replication fork collisions that are marked by chromosome-wide, strand-biased occurrence of RPA-bound single-stranded DNA. Low-level, sporadic induction of G1 replication induced an identical response, indicating findings from synthetic systems are applicable to naturally occurring scenarios of unscheduled replication initiation by G1/S deregulation.

2021-09-07 | GSE182203 | GEO

Cyclin D:Cdk4/6 Activates Rb in Early G1 Phase by Mono-Phosphorylation

Project description:The retinoblastoma tumor suppressor protein (Rb) regulates early G1 phase checkpoints, including the DNA damage response, as well as cell cycle exit and differentiation. The widely accepted model of G1 cell cycle progression proposes that cyclin D:Cdk4/6 partially inactivates the Rb tumor suppressor during early G1 phase by progressive multi-phosphorylation, termed hypo-phosphorylation, resulting in release of E2F transcription factors. However, this model remains largely unproven biochemically and the biologically active form(s) of Rb remains unknown. Here we find that Rb is un-phosphorylated in G0 cells and becomes exclusively mono-phosphorylated throughout all of early G1 phase by cyclin D:Cdk4/6. Early G1 phase mono-phosphorylated Rb is composed of 14 independent isoforms that are all targeted by the E1a oncoprotein, but each shows a preferential binding pattern to specific E2F1-4 transcription factors. At the late G1 Restriction Point, cyclin E:Cdk2 inactivates Rb by a quantum hyper-phosphorylation (>12 phosphates/Rb). Cells undergoing a DNA damage response activate cyclin D:Cdk4/6 to generate mono-phosphorylated Rb that regulates global transcription. In contrast, a non-phosphorylatable ?Cdk-Rb allele was non-functional for regulating a DNA damage response, but functional for driving cell cycle exit and differentiation during myogenesis. These observations fundamentally change our understanding of G1 cell cycle progression and show that there is no progressive multi-phosphorylation or hypo-phosphorylation inactivation of Rb during early G1 phase by cyclin D:Cdk4/6. Instead, cyclin D:Cdk4/6 generates functionally active, mono-phosphorylated Rb that is the only Rb isoform present in cells during early G1 phase.

2014-04-03 | GSE56453 | GEO

poly A+ RNA sequencing of cell cycle-synchronized RNA from U2OS cells

Project description:We performed paired-end poly A+ RNA sequencing using total RNA isolated from U2OS cells that are synchronised into G1, G1/S, S, G2 and M phase of cell cycle.

2020-10-27 | GSE143275 | GEO

High-throughput capture of cis-rearrangement and trans-rearrangement sequence [LAM-HTGTS]

Project description:Cell cycle is a major determinant of DNA double-strand break (DSB) repair pathway choice with homologous recombination (HR) that is most active in S phase cells and non-homologous end-joining (NHEJ) that dominates in G1 phase cells. A third less well-defined mechanism, 'alternative end-joining', has been shown to promote error-prone repair in NHEJ- or HR-deficient cells. Here, we have used a physiologic system of NHEJ-mediated genomic rearrangements induced by the site-specific RAG1/2 endonuclease in G1 cells to investigate the fate of unrepaired G1 DSBs upon entry into the cell cycle. We show that, in the absence of XRCC4, alternative end-joining rescues RAG-induced DSB repair and promotes chromosome translocations upon G1 cell cycle exit.

2020-08-24 | GSE138136 | 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