Transcriptome analysis of Y79 retinoblastoma cells upon Lysyl oxidase propeptide (LOX-PP) overexpression
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PROVIDER: PRJNA489199 | ENA |
REPOSITORIES: ENA
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Project description:Lysyl oxidase (LOX) is an copper dependent amine oxidase enzyme involved in cross linking of collagens and elastins. Lysyl oxidase propeptide (LOX-PP) is 18 kDa region cleaved during maturation of LOX and its anti-tumorigenic role were studied in various cancers. The effect of LOX-PP overexpression in retinoblastoma cancer cells (Y79) using transient transfection of LOX-PP gene accessed for global gene deregulations. The analysis resulted in RB cancer cell death through deregulation of retinoblastoma in cancer, cell cycle, apoptosis, focal adhesion-PI3K-AKT signaling and DNA repair mechanism pathway. Further validations were done using RT-PCR and western blot analysis. Our results provide evidence that inducing apoptosis through AKT-NFκB signaling.
2019-09-01 | GSE119413 | GEO
Project description:In this study we show that lysyl oxidase (LOX), an enzyme involved in maintaining structural integrity of the extracellular matrix, is expressed at low levels in Ewing sarcoma cells and primary tumors and is downregulated by the EWS/FLI1 oncoprotein characteristic of these tumors. Using a doxycycline inducible system to restore LOX expression in an Ewing sarcoma derived cell line, we show that LOX displays tumor suppressor activities. Interestingly, we show that the tumor suppressor activity resides in the propeptide domain of LOX (LOX-PP), an N-terminal domain produced by proteolytic cleavage during the physiological processing of LOX. Finally, we show that LOX-PP inhibits ERK/MAPK signalling pathway, and that many pathways involved in cell cycle progression were significant deregulated by LOX-PP, providing a mechanistic explanation to the cell proliferation inhibition observed upon LOX-PP expression. In summary, our observations indicate that deregulation of the LOX gene participates in Ewing sarcoma development and identify LOX-PP as a new therapeutic target for one of the most aggressive paediatric malignancies. These findings suggest that therapeutic strategies based in the administration of LOX propeptide or functional analogues could be useful in the treatment of this devastating paediatric cancer.
2013-12-31 | GSE46407 | GEO
Project description:In this study we show that lysyl oxidase (LOX), an enzyme involved in maintaining structural integrity of the extracellular matrix, is expressed at low levels in Ewing sarcoma cells and primary tumors and is downregulated by the EWS/FLI1 oncoprotein characteristic of these tumors. Using a doxycycline inducible system to restore LOX expression in an Ewing sarcoma derived cell line, we show that LOX displays tumor suppressor activities. Interestingly, we show that the tumor suppressor activity resides in the propeptide domain of LOX (LOX-PP), an N-terminal domain produced by proteolytic cleavage during the physiological processing of LOX. Finally, we show that LOX-PP inhibits ERK/MAPK signalling pathway, and that many pathways involved in cell cycle progression were significant deregulated by LOX-PP, providing a mechanistic explanation to the cell proliferation inhibition observed upon LOX-PP expression. In summary, our observations indicate that deregulation of the LOX gene participates in Ewing sarcoma development and identify LOX-PP as a new therapeutic target for one of the most aggressive paediatric malignancies. These findings suggest that therapeutic strategies based in the administration of LOX propeptide or functional analogues could be useful in the treatment of this devastating paediatric cancer. A673 cells derived from Ewing sarcoma were genetically enginereed to express LOX-PP upon doxycycline stimulation (72 hours). Three independent experiments from control cells and three independent experiments from A673 cells expressing LOX-PP were done. Gene expression profile in A673 cells expressing LOX-PP vs control cells were compared.
2013-12-31 | E-GEOD-46407 | biostudies-arrayexpress
Project description:miRNA profiling of curcumin treated Y79 cells with untreated Y79 cells (control). Aim of the study to see whether any oncogenes or tumor suppressor genes are regulated on curcumin treatment in Y79 cells.
2010-04-01 | GSE21126 | GEO
Project description:The proteins secreted from Y79 retinoblastoma cell line were analyzed by the GeLC-MS/MS approach.
2024-01-26 | PXD039515 | Pride
Project description:PurposeRetinoblastoma (RB) caused by the mutation of the RB1 gene is one of the most common ocular malignancies in children The propeptide region of lysyl oxidase (LOX), the enzyme involved in the cross-linking of collagen and elastin, has been identified to be anti-tumorigenic in various cancers. However, this role of lysyl oxidase propeptide (LOX-PP) in RB is still elusive. This study aims to identify the anti-tumorigenic effect of LOX-PP in human Y79 RB cells.MethodsLOX-PP was overexpressed in Y79 RB cells, and differential gene expression was assessed by microarray followed by pathway analysis using transcriptome analysis console (TAC) software. Additionally, cell proliferation was studied by PrestoBlue assay, and DNA content was evaluated by cell cycle and apoptosis assays. The pro-apoptotic and anti-proliferative mechanisms induced by the overexpression of/exogenously added LOX-PP was evaluated by western blotting and real-time PCR.ResultsThe expression of the LOX-PP transcript was significantly decreased in Y79 RB cells compared to human retinal endothelial cells. Gene expression analysis in LOX-PP overexpressed Y79 RB cells showed deregulation of pathways involved in apoptosis, cell cycle, focal adhesion-PI3K-AKT signaling, and DNA repair mechanisms. Interestingly, LOX-PP overexpressed Y79 RB cells showed significantly increased apoptosis, decreased proliferation, and cell cycle arrest at S-phase with a concordant reduction of proliferative cell nuclear antigen and Cyclin D1 protein expressions. Moreover, pAKT (S473) was significantly downregulated in Y79 RB cells, which decreased NFκB leading to significantly reduced BCL2 expression.ConclusionsOur results demonstrate the anti-tumorigenic effect of LOX-PP in Y79 RB cells by inducing apoptosis and decreasing proliferation. This effect was mediated by the downregulation of AKT signaling. These results suggest that LOX-PP can be explored as a therapeutic molecule in RB.
| S-EPMC10784223 | biostudies-literature
Project description:The proteins on the surface of Y79 retinoblastoma cell line were analyzed by cell surface biotinylation and streptavidin affinity purification.
2024-01-26 | PXD039517 | Pride
Project description:Lysyl oxidase is an extracellular enzyme essential for crosslinking elastin and collagen. Mice that do not express Lox have 60% and 40% reductions in elastin-specific and collagen-specific crosslinks, respectively. Mutations in LOX are associated with thoracic aortic aneurysm and dissection (TAAD). Lysyl oxidase knockout mice dye perinatally with ruptured diaphragm, tortuous arteries, and TAAD This is the first study to analyze the mechanical and genetic changes induced by the absence of lysyl oxidase in the thoracic aorta, and may provide new therapeutic targets relevant for the pathogenesis of thoracic aortic aneurysms and dissections
2016-10-28 | GSE89227 | GEO
Project description:miRNA profiling of curcumin treated Y79 cells with untreated Y79 cells (control). Aim of the study to see whether any oncogenes or tumor suppressor genes are regulated on curcumin treatment in Y79 cells. Agilent one-color experiment,Organism: Human ,Agilent-019118 Human miRNA Microarray 2.0 G4470B , Labeling kit: Agilent miRNA labeling reagent and Hybridization Kit Cat # 5190-0408
2010-04-01 | E-GEOD-21126 | biostudies-arrayexpress
Project description:Primary murine lung fibroblasts were transfected with either control (scrambled) or sequence-specific siRNA against Lysyl oxidase (Lox), Lysyl oxidase-like (Loxl1) or Lysyl oxidase-like 2 (Loxl2) genes. Cells were harvested 48 hours after the transfection. Multiple changes in gene expression were found in the corrected p values in this microarray study.
2016-10-25 | GSE89121 | GEO