C1Q + TPP1 + macrophages promote colon cancer progression through SETD8-driven p53 methylation.
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1090469 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28410882_1.fastq.gz | Fastqsanger.gz | |||
| SRR28410882_2.fastq.gz | Fastqsanger.gz | |||
| SRR28410883_1.fastq.gz | Fastqsanger.gz | |||
| SRR28410883_2.fastq.gz | Fastqsanger.gz | |||
| SRR28410884_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 8 |
Similar Datasets
Project description:In many tumors, the tumor suppressor TP53 (p53) is not mutated, but experiences functional inactivation. Notwithstanding, restoring p53 function emerges as an appealing therapeutic approach for tumors exhibiting wild-type p53 (p53WT). However, the mechanisms underlying the functional inactivation of p53 in these tumors remain poorly understood. Previously, we identified SETD8 as a critical suppressor of p53 activity in neuroblastomas. SETD8 is the sole known enzyme that mono-methylates p53 on lysine 382 (p53K382me1), resulting in the inhibition of its pro-apoptotic and growth-arresting functions. In this study, we observed high expression levels of SETD8 and p53K382me1 in 185 colorectal cancer (CRC) tissue samples, being negatively associated with patient survival probability. Significantly, the expression of p53K382me1 resulted confined to colorectal cancer stem cells and tumor-associated macrophages (TAM) in tissues obtained from CRC patients. Within CRC patient cohorts, high expression of p53K382me1 levels in both stem and immune cells predict decreased survival probability. The SETD8-mediated inactivation of p53 through p53K382me1 may serve as an early requirement for tumor initiation, particularly in inflammation-induced cancers, and as a functional biomarker and therapeutic target in advanced CRCs
2025-04-03 | GSE262144 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE36749: Mutant p53 cooperates with ETS2 to promote etoposide resistance [ChIP-Seq] GSE36751: Mutant p53 cooperates with ETS2 to promote etoposide resistance [ChIP-chip] Refer to individual Series
2012-05-02 | E-GEOD-36752 | biostudies-arrayexpress
Project description:We have data from a previous microarray experiment which shows that C1q elicits macrophages to express genes important for clearance of dead (apoptotic) cells. In this experiment we want to determine the signaling mechanism by which C1q is turning on macrophage gene expression. For our control (sample 1-3) we heated C1q to denature it so it is inactive. We also want to know which portion of C1q is responsible for activation the macrophage so we generated C1qtails (samples 4-5). We also have macrophages treated with the whole C1q molecule (7-9). And finally we have a cell line (J774) treated with C1q but does not activate the cells (samples 10-12). Bone marrow derived macrophages or J774 cells were adhered to heat inactivated C1q, C1q tails or C1q for 18 hours. Cells were harvested and RNA was isolated and converted to double stranded cDNA and subsequently labeled and hybridized onto NimbleGen mouse gene expression array [100718_MM9_EXP] using Nimblegen Hybridization system 4 according to manufacturerM-bM-^@M-^Ys instructions (Roche)
2014-07-10 | E-GEOD-48619 | biostudies-arrayexpress
Project description:p53 is a pivotal tumor suppressor and a major barrier against cancer. We now report that silencing of the Hippo pathway tumor suppressors LATS1 and LATS2 in non-transformed mammary epithelial cells reduces p53 phosphorylation and increases its association with the p52 NF-κB subunit. Moreover, it partly shifts p53’s conformation and transcriptional output towards a state resembling cancer-associated p53 mutants, and endow p53 with the ability to promote cell migration. Notably, LATS1 and LATS2 are frequently downregulated in breast cancer; we propose that such downregulation might benefit cancer by converting p53 from a tumor suppressor into a tumor facilitator.
2018-10-25 | PXD003120 | Pride
Project description:We have data from a previous microarray experiment which shows that C1q elicits macrophages to express genes important for clearance of dead (apoptotic) cells. In this experiment we want to determine the signaling mechanism by which C1q is turning on macrophage gene expression. For our control (sample 1-3) we heated C1q to denature it so it is inactive. We also want to know which portion of C1q is responsible for activation the macrophage so we generated C1qtails (samples 4-5). We also have macrophages treated with the whole C1q molecule (7-9). And finally we have a cell line (J774) treated with C1q but does not activate the cells (samples 10-12).
2014-07-10 | GSE48619 | GEO
Project description:p53 is a pivotal tumor suppressor and a major barrier against cancer. We now report that silencing of the Hippo pathway tumor suppressors LATS1 and LATS2 in non-transformed mammary epithelial cells reduces p53 phosphorylation and increases its association with the p52 NF-?B subunit. Moreover, it partly shifts p53âs conformation and transcriptional output towards a state resembling cancer-associated p53 mutants, and endow p53 with the ability to promote cell migration. Notably, LATS1 and LATS2 are frequently downregulated in breast cancer; we propose that such downregulation might benefit cancer by converting p53 from a tumor suppressor into a tumor facilitator. MCF10A cells transfected with siRNA against LATS1/2 alone, p53 alone or LATS1/2 and p53 together. Two independent MCF10A batches provided biological replicates
2015-12-11 | E-GEOD-74493 | biostudies-arrayexpress
Project description:Purpose: The intergration of genetic and chemical screens identified SETD8 as a new druggable target in neuroblastoma tumor. The goal of this study is to evaluate the transcriptome profiling (RNA-seq) of Neuroblastoma cell lines after genetic and pharmacological inhibition of SETD8. Methods: mRNA profiles of NB cells after genetic and pharmacological inhibition of SETD8 were generated by deep sequencing in duplicate with Ilumina HiSeq2500 using Illumina TruSeq V4. The sequence reads were analyzed with software Trimmomatic, STAR and edgeR to determine the differetially expressed genes. qRT–PCR validation was performed using SYBR Green assays. Results: About 60 million sequence reads per sample were mapped to the human genome (hg19). Approximately 10% of the transcripts showed differential expression between the control and the treated samples, with a fold change ≥1.5 and p value <0.05. Altered expression of 12 genes was confirmed with qRT–PCR, demonstrating the high degree of sensitivity of the RNA-seq method. Hierarchical clustering of differentially expressed genes uncovered several as yet uncharacterized genes that may contribute to SETD8 function. Conclusions: Our study identifies SETD8 as a new therapeutic target in Neuroblastoma tumor. RNA-seq transcriptome analyses and functional studies revealed that SETD8 ablation rescued the proapoptotic and cell-cycle arrest functions of p53 through reactivation of the p53 canonical pathway by decreasing p53k382me1.
2017-01-09 | GSE81626 | GEO
Project description:P53 mutation is closely associated with the occurrence and progression of colon cancer. In this project, we did crotonylomics sequencing by using human colon cancer homologous cell line pair-HCT116+/+(with wild type p53) and HCT116-/- (with null p53). Crotonylomics sequencing results showed that p53 deficiency regulated crotonylation of non-histone proteins.
2024-05-22 | PXD047258 | Pride
Project description:Purpose: Over the past few years, the distinction between left- and right-sided colon cancer has been brought into focus. Right-sided tumor location was associated with an inferior overall survival and progression-free survival. We aimed to perform a detailed analysis of the diversity in exosomes between left- and right-sided colon cancer using quantitative proteomics. Experimental Design: We isolated exosomes from left- and right-sided colon cancer patients and healthy volunteers and treated colorectal cancer cell line with serum-derived exosomes. Then we performed quantitative proteomics analysis of the serum-derived exosomes and cell line treated with exosomes, respectively. Results: The expression profile of the serum exosome proteome in patients with right-sided colon cancer is different from patients with left-sided colon cancer. Serum-derived exosomes of right-sided colon cancer promote metastasis via up-regulation of extracellular matrix-related proteins, especially proteoglycans like SPARC and glycoprotein like LRG1. Exosomal SPARC and LRG1 were closely correlated with progression-free survival. Conclusions: Proteomic analysis identified different exosomal protein profiling between left- and right-sided colon cancer. Serum-derived exosomes of right-sided colon cancer promote metastasis via overexpression of SPARC and LRG1.
2019-11-25 | PXD012304 | Pride
Project description:p53 is a pivotal tumor suppressor and a major barrier against cancer. We now report that silencing of the Hippo pathway tumor suppressors LATS1 and LATS2 in non-transformed mammary epithelial cells reduces p53 phosphorylation and increases its association with the p52 NF-?B subunit. Moreover, it partly shifts p53’s conformation and transcriptional output towards a state resembling cancer-associated p53 mutants, and endow p53 with the ability to promote cell migration. Notably, LATS1 and LATS2 are frequently downregulated in breast cancer; we propose that such downregulation might benefit cancer by converting p53 from a tumor suppressor into a tumor facilitator.
2015-12-11 | GSE74493 | GEO