ACC-MESO1 cells: Control shRNA vs USP22 shRNA
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE104929 | GEO | 2018/10/01
REPOSITORIES: GEO
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Project description:USP22 plays oncogenic roles and in order to identify the molecular mechanism of USP22 to promote tumorigenesis, RNA-seq was performed on Huh7 cells with or without USP22.
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Project description:ACC-MESO1 cells: Control shRNA vs USP22 shRNA
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Project description:RNA-seq analysis of sorted Usp22-WT and Usp22-KO tumor cells from subcutaneously implanted mouse pancreatic tumors
2019-11-08 | GSE140088 | GEO
Project description:USP22 overexpression is observed in several human cancers and is correlated with poor patient outcomes. The molecular basis underlying this correlation is not clear. USP22 is the catalytic subunit of the deubiquitylation module in the SAGA histone modifying complex, which regulates gene transcription. Our previous work demonstrated that loss of USP22 in mice leads to decreased expression of several components of receptor tyrosine kinase and TGFβ signaling pathways. To determine whether these pathways are upregulated when USP22 is overexpressed, we created a mouse model that expresses high levels of USP22 in all tissues. Phenotypic characterization of these mice revealed over branching of the mammary glands in females. Transcriptomic analyses indicate upregulation of key pathways involved in mammary gland branching in mammary epithelial cells derived from the USP22 overexpressing mice, including estrogen receptor, ERK/MAPK and TGFβ signaling. However, USP22 overexpression did not lead to increased tumorigenesis in any tissue. Our findings indicate that elevated levels of USP22 are not sufficient to induce tumors but it may enhance signaling abnormalities associated with oncogenesis.
2021-08-13 | GSE180005 | GEO
Project description:Dynamic control of ubiquitination by deubiquitinating enzymes is essential for almost all biological processes. Ubiquitin-specific peptidase 22 (USP22) is part of the SAGA complex and catalyzes the removal of monoubiquitination from histone H2B, thereby regulating gene transcription. However, novel roles for USP22 have recently emerged, such as tumor development and cell death. Apart from apoptosis, the relevance of USP22 in other programmed cell death pathways still remains unclear. Here, we describe a novel role for USP22 in controlling necroptotic cell death in a variety of tumor cell lines. Loss of USP22 expression significantly delays TNF/Smac mimetic/zVAD.fmk (TBZ)-induced necroptosis, without affecting TNF-mediated NF-B activation or extrinsic apoptosis. Mass-spectrometric ubiquitin remnant profiling identified lysine 518 of Receptor-interacting protein kinase 3 (RIPK3) as USP22-dependent ubiquitination target during necroptosis induction. Mutation of K518 in RIPK3 reduced necroptosisassociated RIPK3 ubiquitination and amplified necrosome formation and necroptotic cell death. In conclusion, we identify a novel role of USP22 in necroptosis and further elucidate the relevance of ubiquitination as crucial regulator of necroptotic cell death.
2021-05-03 | PXD020909 | Pride
Project description:Mouse ESCs depleted of the epigenetic modifying enzyme Usp22 fail to differentiate properly. Ectopic expresison of Usp22 results in spontaneous differnetiation. In order to understand the transcriptional program underlying this biological defect, whole genome expression analysis was performed. E14 mESCs were infected with lentivirus containing shRNA targeting Usp22 or control (Luc). RNA was extracted from both samples and subjected to expression analysis by affymetrix array.
2013-05-15 | E-GEOD-42934 | biostudies-arrayexpress
Project description:Somatic cells can be reprogrammed to induced pluripotent stem cells (iPSCs) by overexpressing OCT4, SOX2, KLF4 and MYC. Although this cell fate transition is a slow and inefficient process, inhibiting several epigenetic barriers has shown to facilitate it. A previously employed epigenetic focused CRISPR-Cas9-mediated knockout screen during reprogramming uncovered novel human somatic cell reprogramming barriers. Here, I showed that USP22, target for gRNAs that were enriched in iPSCs from the screen, is a barrier for reprogramming and its loss is compatible with iPSC generation. Overexpressing wild-type or deubiquitinase mutant (C185A) USP22 in knockout background could rescue the phenotype. Additionally, knocking out other SAGA deubiquitinase subunits, ENY2 and ATXN7L3 did not increase the reprogramming efficiency. Mechanistically, we showed that USP22 loss upregulates an important pluripotency-related transcription factor, SOX2, expression even as early as 3 days after OSKM expression. We hypothesized that USP22 downregulates pluripotency-related gene expression during reprogramming independent from its SAGA integration and deubiquitinase activity. To address this, I will repeat rescuing USP22 knockout phenotype in reprogramming by overexpressing mutant versions of USP22 including K129R (acetyl inhibited) and HHAA (deubiqutinase). Additionally, I will check the expression of pluripotency-related genes at early time points of reprogramming upon USP22 knockout by transcriptome profiling. Lastly, I will generate USP22 knockout iPSC lines to force them to differentiation to observe if they have any problem with pluripotency exit. This work will establish a mechanistic understanding for the role USP22 play on both human somatic cell reprogramming, pluripotency and differentiation.
2023-07-31 | GSE225151 | GEO
Project description:Mouse ESCs depleted of the epigenetic modifying enzyme Usp22 fail to differentiate properly. Ectopic expresison of Usp22 results in spontaneous differnetiation. In order to understand the transcriptional program underlying this biological defect, whole genome expression analysis was performed.
2013-05-15 | GSE42934 | GEO
Project description:Glioblastoma (GBM) is the most common and aggressive primary brain tumor with limited therapeutic options, possibly because of the highly tumorigenic subpopulations of stem cell-like cells. Mechanisms that sustain cancer stem cells are crucial to tumor progression. The polycomb group protein BMI1 (BMI1 proto-oncogene, polycomb ring finger) maintains cancer hallmarks including the glioblastoma stem-like cell (GSC) state. Ubiquitin-specific protease 22 (USP22) is highly expressed in and required for the maintenance of cancer stem cells (CSCs). Previously, we observed that forced expressed microRNA-218 in glioblastoma cells led to suppressed BMI1 expression. However, the pathways engaged by USP22 or driving BMI1 accumulation in GSCs remained elusive. Here, we found USP22 to be a novel deubiquitylase of BMI1. USP22 directly deubiquitylates and stabilizes BMI1. USP22 protein levels are elevated in tumor neurosphere. USP22 depletion induces BMI1 destabilization, and results in the inhibition of GSCs self-renewal by regulating a broad range of genes involved in glioma stemness and progression. Xenograft analyses using U87MG cells showed that both USP22 and BMI1 depletion attenuated tumor growth. Clinically, the expression levels of USP22 and BMI1 were positively correlated with those common targets like POSTN, HEY2, or PDGFRA and inversely correlated with ATF3 in human glioblastoma specimens. Taken together, our data reveals that USP22 functions as a novel deubiquitylase of BMI1 and inhibits self-renewal of GSCs by stabilizing BMI1. These findings also indicate that the USP22-BMI1 axis has a critical role in glioma tumorigenesis and that targeting the axis may provide a new therapeutic approach for human glioblastoma.
2017-01-01 | GSE89239 | GEO
Project description:Within the context of the DUB module in the SAGA complex, USP22 is involved in transcriptional elongation through the regulation of H2AK119ub1 and H2BK120ub1. However, up till now, the spectrum of USP22-regulated target genes largely remains unclear, partially due to organism-, cell- and context-dependent redundancy in alternative DUBs that might compensate for loss of USP22. To understand which genes are regulated by USP22, we profiled USP22-dependent changes in gene expression in the human intestinal epithelial cell (hIEC) line HT-29.
2022-08-22 | GSE190036 | GEO