Effect of USP10 knockout using CRISPR on gene expression in MCF7 breast cancer cells
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PROVIDER: PRJNA1291091 | ENA |
REPOSITORIES: ENA
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Project description:Using a genome wide shRNa screen we identified the deubiqutinating enzyme USP10 as a potent regualtor of AKT activity. To validate our findings we performed RNA-Seq on MCF7 cells with or without USP10 depletion. In line with our previous observations we demonstrate that PI3k-AKT-mTOR pathway activation is downregualted in our USP10 knockout cells. Our later work shows that this function is mediated through a USP10-GSK3B mediated mechanism resulting in PTEN inactivation. Taken together this work demonstrates the imprtance of USP10 in PI3K pathway regualtion.
2025-07-28 | GSE302500 | GEO
Project description:To further explore gene expression in neonatal mice with Usp10 gene knockout, we have employed whole genome microarray expression profiling as a discovery platform to identify the pathways or biological processes with the potential to explain the cause of postnatal death of Usp10 knockout mice. Kidney tissues from Usp10 knockout neonates and their littermates were used to be the samples to explore.
2022-03-15 | GSE198574 | GEO
Project description:USP10 is an important factor in the progression of colorectal cancer, as inhibition or silencing of USP10 attenuates the aggressive phenotype. USP10 regulates sensitivity to the two widely used EGFR inhibitors gefitinib and osimertinib. Mechanistically, we show that USP10 mediates its effects via the phosphatase INPP4B, which regulates the downstream PI3K/AKT/mTOR signaling pathway. Thus, our study demonstrates for the first time a novel link between USP10 and response to EGFR-targeted therapy.
2025-05-07 | PXD052294 | Pride
Project description:Notch signaling is critical for vascular morphogenesis by co-determining the sprouting behavior of endothelial cells. Here, we investigate the function of ubiquitin-specific peptidase 10 (USP10) in regulation of the turnover of the NOTCH1 intracellular domain. HUVEC were transfected with scrambled or USP10 targeting siRNA and then stimulated by treatment with DLL4 or control. RNA for analysis was isolated after 24 hours of DLL4 stimulation.
2019-04-26 | E-MTAB-7774 | biostudies-arrayexpress
Project description:The contribution of deubiquitylating enzymes to b-Catenin stabilisation in intestinal stem cells and colorectal cancer (CRC) is poorly understood. Here, we report the deubiquitylase USP10 as APC-truncation- specific regulator enhancer of b-Catenin stability, potentiating WNT signalling pathway in CRC and cancer stem cells. Mechanistically, interaction studies in various CRC cell lines and in vitro binding studies, together with computational modelling, revealed that USP10 binding to b-Catenin is mediated via its USP10 unstructured N-terminus and requires truncated in the absence of full-length APC. Notably, loss of USP10 in CRISPR engineered intestinal organoids reduces tumorigenic properties of CRC cells and organoids, and blocks the super competitor-properties of APC-mutated intestinal cells, elicits induces the expression of differentiation genes, and opposes the APC-truncated phenotype in an intestinal hyperplasia model of D.melanogaster. Taken together, our findings reveal USP10s role in intestinal tumourigenesis by stabilising b-Catenin, leading to aberrant WNT signalling, enhancing cancer cell stemness and implicate the DUB USP10 as a cancer specific therapeutic vulnerability in Apc truncated CRC.
2024-01-01 | GSE226364 | GEO
Project description:Aims: Cardiac fibroblasts (CFs) play a crucial role in cardiac remodelling, which is a common cause of heart failure (HF). However, the molecular mechanisms underlying the fibroblast-to-myofibroblast transition remain largely unknown. Foxm1 is well known in various cardiopulmonary pathologies. However, Foxm1-driven CF activation in the progression of cardiac remodelling to HF remains to be investigated. Methods: Changes in Foxm1 expression were assessed in samples from patients with HF and mice with transverse aortic constriction (TAC)-induced cardiac remodelling. Pharmacologic antagonist FDI-6 was used to explore the effects of Foxm1 inhibition on post-TAC outcomes. Tcf21-Cre and PostnMCM were used to evaluate Foxm1 loss- and gain-of-function in CFs and myofibroblasts, respectively. Cardiac function and remodelling were examined by echocardiography and histological analysis. Foxm1 downstream target genes were identified by mass spectrometry (MS) and transcriptomic analysis. Post-translational regulation was evaluated by in vitro chromatin immunoprecipitation, co-immunoprecipitation, and ubiquitination assays. Pharmacological inhibition of Usp10 or knockout of p38γ in vivo verified the signalling pathway by which Foxm1 regulated cardiac remodelling. Results: Foxm1 was upregulated in human HF samples as well as in the mouse cardiac remodelling model. CFs were the primary cell type responsible for Foxm1 upregulation. Foxm1 pharmacological inhibition or genetic knockout in CFs or myofibroblasts significantly attenuated TAC-induced cardiac remodelling and HF. Conversely, conditional overexpression of Foxm1 in CFs or myofibroblasts resulted in more severe pathological cardiac remodelling and dysfunction. Combined RNA-sequencing and MS analysis revealed that Foxm1 promoted Usp10 expression by binding to its promoter. Usp10 interacted with p38γ, resulting in p38γ deubiquitination and thus influencing the downstream p38 mitogen-activated protein kinase (MAPK) signalling pathway. Pharmacological inhibition of Usp10 or genetic knockout of p38γ ameliorated the exacerbated TAC-induced cardiac remodelling in mice with myofibroblast-specific Foxm1 overexpression. Conclusion: Our findings reveal an essential role of Foxm1 in CF activation during cardiac remodelling. These results suggest that targeting the Foxm1/Usp10/p38γ MAPK axis may represent a new potential therapeutic strategy against pathological cardiac remodelling and HF.
2024-03-10 | PXD050300 | Pride
Project description:Development of gene expression signatures for neonatal tissues of mice with Usp10 gene knockout
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Project description:MLL3 inactivation mutations occurs frequently in human breast cancer. To understand the function of MLL3 inactivation, we compared the gene expression profiles of the vector control (WT) and Mll3-knockout MCF7 cells generated by CRISPR-CAS9. Affymetrix human Gene 2.0ST arrays were used for microarray.
2022-10-08 | GSE171445 | GEO
Project description:CRISPR knockout (CRISPR KO) screens on the PC cell line
| PRJNA1173604 | ENA
Project description:This project aims to compare gRNA design algorithms and single- versus dual-targeting using a benchmark CRISPR-knockout library composed of gRNAs targeting essential and non-essential genes.
2025-02-12 | E-MTAB-13981 | biostudies-arrayexpress