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RNAseq analysis for transcriptomes of colon cancer cell line HCT116 upon p53 and/or iASPP knockdown with or without nutlin treatment

ABSTRACT: The tumor suppressor p53 plays a critical role in the cellular response to various stresses, including DNA damage, hypoxia, nutrition starvation, and oncogene activation. However, wild-type p53 function was largely impaired in cancer cells, one of the reasons is the inhibition by p53 negative regulating proteins (iASPP, MDM2 etc.). To globally evaluate the transcriptome inhibited by iASPP and the potent synergy of co-inhibiting MDM2, we performed RNAseq analysis in colon cancer cell line HCT116 upon p53 or iASPP knockdown with or without Nutlin-3 treatment.

ORGANISM(S): Homo sapiens

PROVIDER: GSE139546 | GEO | 2022/10/29

REPOSITORIES: GEO

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Selective and direct p53 inhibition by iASPP

Project description:We performed p53 ChIP-seq analysis of Nutlin-treated HCT116 cells to identify high-confident p53 regulated targets. And we performed ChIP-seq using an anti-p53 antibody in HCT116 cells treated with control or iASPP RNAi to identify iASPP regulated p53 targets.

2019-09-23 | GSE113338 | GEO

p53 ChIP-seq in Nutlin-treated HCT116, MCF7, and SJSA cell lines

Project description:To identify genomic loci occupied by p53, we performed p53 ChIP-seq analysis of colorectal carcinoma cell line HCT116, breast carcinoma line MCF7, and osteosarcoma line SJSA treated with MDM2 inhibitor Nutlin.

2017-08-22 | GSE86164 | GEO

Total RNA-seq from HCT116, MCF7 and SJSA cell lines treated with DMSO and Nutlin

Project description:To determine effects of p53 activation on steady-state mRNA levels, we performed RNA-seq analysis of colorectal carcinoma cell line HCT116 (p53+/+ and p53 -/-), breast carcinoma line MCF7, and osteosarcoma line SJSA treated with MDM2 inhibitor Nutlin.

2017-08-22 | GSE86221 | GEO

RNAseq from polysomal RNA harvested from HCT116, MCF7 and SJSA cell lines treated with DMSO and Nutlin

Project description:To determine effects of p53 activation on levels of RNA associated with polysomes, we performed RNA-seq analysis of colorectal carcinoma cell line HCT116, breast carcinoma line MCF7, and osteosarcoma line SJSA treated with MDM2 inhibitor Nutlin.

2017-08-22 | GSE86219 | GEO

Cooperation of Nutlin-3a and a Wip1 inhibitor to induce p53 activity

Project description:Targeting the Mdm2 oncoprotein by drugs has the potential of re-establishing p53 function and tumor suppression. However, Mdm2-antagonizing drug candidates, e. g. Nutlin-3a, often fail to abolish cancer cell growth sustainably. To overcome these limitations, we inhibited Mdm2 and simultaneously a second negative regulator of p53, the phosphatase Wip1/PPM1D. When combining Nutlin-3a with the Wip1 inhibitor GSK2830371 in the treatment of p53-proficient but not p53-deficient cells, we observed enhanced phosphorylation (Ser 15) and acetylation (Lys 382) of p53, increased expression of p53 target gene products, and synergistic inhibition of cell proliferation. Surprisingly, when testing the two compounds individually, largely distinct sets of genes were induced, as revealed by deep sequencing analysis of RNA. In contrast, the combination of both drugs led to an expression signature that largely comprised that of Nutlin-3a alone. Moreover, the combination of drugs, or the combination of Nutlin-3a with Wip1-depletion by siRNA, activated p53-responsive genes to a greater extent than either of the compounds alone. Simultaneous inhibition of Mdm2 and Wip1 enhanced cell senescence and G2/M accumulation. Taken together, the inhibition of Wip1 might fortify p53-mediated tumor suppression by Mdm2 antagonists.

2016-05-02 | GSE80716 | GEO

Genome-wide map of p53 binding sites by ChIP-seq in human lymphoblastoid cell lines treated with nutlin-3

Project description:We have used chromatin immune-precipitation with parallel sequencing (ChIP-Seq) technology to identify genome-wide p53 binding in human lymphoblastoid cell lines treated with a MDM2 inhibitor nutlin-3 ChIP-Seq analysis of p53 binding sites in human lymphoblastoid cells treated with nutlin-3 or vehicle

2013-10-23 | E-GEOD-46992 | biostudies-arrayexpress

Nutlin-3 treatment of B-CLL

Project description:Background: p53 plays a key role in determining the clinical features of B cell chronic lymphocytic leukemia (CLL). Disruption of p53 by point mutations, deletion at 17p13, or both, occurs in a fraction of cases at diagnosis and predicts poor survival and chemorefractoriness. In cells with functional p53, p53 activity is inhibited through interaction with MDM2. In fact, p53 can be activated upon exposure of cells to inhibitors of p53/MDM2 interaction, like Nutlins. Exposure of CLL cells to Nutlin-3 is effective in raising the levels of p53 protein with subsequent induction of cell cycle arrest and/or apoptosis, independently of the most relevant prognostic markers. Specific gene-sets and GEP were documented to be associated with response or resistance to Nutlin-3 exposure in p53(wt) or p53(del/mut) CLL. These findings may help to identify novel molecular targets for CLL therapy. Aim: to analyze the gene expression profile (GEP) induced by Nutlin-3 exposure in primary CLL cells from p53(wt) and p53(del/mut) cases. Methods: purified cells from 24 PB CLL samples, all characterized for IGHV mutational status, CD38 and ZAP-70 and p53 mutations (16 p53(wt) CLL, 8 p53(del/mut) CLL of which 6 with del17p13 and p53 mutations, 1 with del17p13 alone, and 1 with p53 mutations alone), were exposed to 10 uM Nutlin-3 for 24 hours. GEP was performed using a dual labelling strategy; the differential expression of the below reported genes were validated by quantitative real-time PCR. specific gene-sets and GEP were documented to be associated with response or resistance to Nutlin-3 exposure in p53(wt) or p53(del/mut) CLL. These findings may help to identify novel molecular targets for CLL therapy.

2009-11-11 | GSE18971 | GEO

GRO-seq from HCT116, MCF7 and SJSA cell lines treated with DMSO and Nutlin

Project description:To identify loci with transcriptionally engaged RNA polymerase, we performed GRO-seq analysis of colorectal carcinoma cell line HCT116, breast carcinoma line MCF7, and osteosarcoma line SJSA treated with MDM2 inhibitor Nutlin.

2017-08-22 | GSE86165 | GEO

Interruption of p53-MDM2 Interaction by Nutlin-3a in Human Lymphoma Cell Models Initiates a Cell-Dependent Global Effect on Transcriptome and Proteome Level

Project description:In most lymphomas, p53 signaling pathway is inactivated by various mechanisms independent to p53 gene mutations or deletions. In many cases, p53 function is largely regulated by alterations in the protein abundance levels by the action of E3 ubiquitin-protein ligase MDM2, targeting p53 to proteasome-mediated degradation. In the present study, an integrating transcriptomics and pro-teomics analysis was employed to investigate the effect of p53 activation by a small-molecule MDM2-antagonist, nutlin 3a, on three lymphoma cell models following p53 activation. Our analy-sis revealed a system-wide nutlin 3a-associated effect in all examined lymphoma types, identifying in total of 4037 differentially affected proteins involved in a plethora of pathways, with significant heterogeneity among lymphomas. Our findings include known p53-targets and novel p53 activa-tion effects, involving transcription, translation, or degradation of protein components of path-ways, such as a decrease in key members of PI3K/mTOR pathway, heat-shock response, and gly-colysis, and an increase in key members of oxidative phoshosphorylation, autophagy and mito-chondrial translation. Combined inhibition of HSP90 or PI3K/mTOR pathway with nutlin 3a-mediated p53-activation enhanced the apoptotic effects suggesting a promising strategy against human lymphomas. Integrated omic profiling after p53 activation offered novel insights on the regulatory role specific proteins and pathways may have in lymphomagenesis.

2023-07-30 | PXD009290 | Pride

RNA-seq timecourse of p53 activation with Nutlin-3a in IMR90 cells

Project description:To investigate the dynamics of the p53 response, we treated IMR90 cells with Nutlin-3a, a small molecule that inhibits the interaction between p53 and its inhibitor Mdm2, for 6, 9, or 12 hours.

2020-10-31 | GSE139003 | GEO

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