Similar Datasets
Project description:Osteosarcoma is an aggressive bone tumor that primarily affects children and adolescents. This malignancy is highly aggressive, associated with poor clinical outcomes, and primarily metastasizes to the lungs. Due to its rarity and biological heterogeneity, limited studies on its molecular basis exist, hindering the development of effective therapies. The WW domain-containing oxidoreductase (WWOX) is frequently altered in human osteosarcoma. Combined deletion of Wwox and Trp53 using Osterix1-Cre transgenic mice has been shown to accelerate osteosarcoma development. In this study, we generated a traceable osteosarcoma mouse model harboring the deletion of Trp53 alone (single-knockout) or combined deletion of Wwox/Trp53 (double-knockout) and expressing a tdTomato reporter. By tracking Tomato expression at different time points, we detected the early presence of tdTomato-positive cells in the bone marrow mesenchymal stem cells of non-osteosarcoma-bearing mice (young BM). We found that double-knockout young BM cells, but not single-knockout young BM cells, exhibited tumorigenic traits both in vitro and in vivo. Molecular and cellular characterization of these double-knockout young BM cells revealed their resemblance to osteosarcoma tumor cells. Interestingly, one of the observed significant transcriptomic changes in double-knockout young BM cells was the upregulation of Myc and its target genes compared to single-knockout young BM cells. Intriguingly, Myc-chromatin immunoprecipitation sequencing revealed its increased enrichment on Myc targets, which were upregulated in double-knockout young BM cells. Restoration of WWOX in double-knockout young BM cells reduced Myc protein levels. As a prototype target, we demonstrated the upregulation of MCM7, a known Myc target, in double-knockout young BM relative to single-knockout young BM cells. Inhibition of MCM7 expression using simvastatin resulted in reduced proliferation and tumor cell growth of double-knockout young BM cells. Our findings reveal BM mesenchymal stem cells as a platform to study osteosarcoma and Myc and its targets as WWOX effectors and early molecular events during osteosarcomagenesis.
| S-EPMC10770339 | biostudies-literature
Project description:Osteosarcoma (OS) is an aggressive bone tumor that primarily affects children and adolescents. This malignant tumor is highly aggressive, associated with poor clinical outcomes, and metastasizes mainly to the lungs. Due to its rarity and biological heterogeneity, limited studies of its molecular basis exist, thus hindering the development of effective therapies. WW domain-containing oxidoreductase (WWOX) spans one of the most active and common fragile sites that is frequently altered in human OS. The combined deletion of Wwox and Trp53 using Osterix1-Cre transgenic mice has been shown to accelerate OS development. In this study, we generated a traceable OS mouse model, SKO-Trp53 or DKO-Wwox/Trp53, expressing a tdTomato reporter. By tracking tomato expression at different time points, we detected the early presence of tdTomato-positive cells in the bone marrow (BM) mesenchymal stem cells (MSCs) of non-OS bearing mice, young BM (yBM). We found that DKO yBM cells, but not SKO yBM cells, exhibited tumorigenic traits both in vitro and in vivo. Molecular and cellular characterization of these DKO yBM cells revealed their resemblance to OS tumor cells. Interestingly, one of the observed significant transcriptomic changes in DKO yBM was the upregulation of Myc and its target genes, as compared to SKO yBM cells. Intriguingly, Myc-chromatin immunoprecipitation sequencing (ChIP-Seq) revealed increased enrichment on Myc targets, which were upregulated in DKO yBM cells. Restoration of WWOX in DKO-yBM cells reduced Myc protein levels. As a prototype target, we demonstrated upregulation of MCM7, a known Myc target, in DKO yBM relative to SKO yBM. Inhibition of MCM7 expression using Simvastatin resulted in reduced proliferation and tumor cell growth of DKO yBM cells. Our findings revealed BM-MSCs as a platform to study OS and Myc and its targets as WWOX effectors and early molecular events during osteosarcomagenesis.
2025-10-01 | GSE245605 | GEO
Project description:Osteosarcoma (OS) is an aggressive bone tumor that primarily affects children and adolescents. This malignant tumor is highly aggressive, associated with poor clinical outcomes, and metastasizes mainly to the lungs. Due to its rarity and biological heterogeneity, limited studies of its molecular basis exist, thus hindering the development of effective therapies. WW domain-containing oxidoreductase (WWOX) spans one of the most active and common fragile sites that is frequently altered in human OS. The combined deletion of Wwox and Trp53 using Osterix1-Cre transgenic mice has been shown to accelerate OS development. In this study, we generated a traceable OS mouse model, SKO-Trp53 or DKO-Wwox/Trp53, expressing a tdTomato reporter. By tracking tomato expression at different time points, we detected the early presence of tdTomato-positive cells in the bone marrow (BM) mesenchymal stem cells (MSCs) of non-OS bearing mice, young BM (yBM). We found that DKO yBM cells, but not SKO yBM cells, exhibited tumorigenic traits both in vitro and in vivo. Molecular and cellular characterization of these DKO yBM cells revealed their resemblance to OS tumor cells. Interestingly, one of the observed significant transcriptomic changes in DKO yBM was the upregulation of Myc and its target genes, as compared to SKO yBM cells. Intriguingly, Myc-chromatin immunoprecipitation sequencing (ChIP-Seq) revealed increased enrichment on Myc targets, which were upregulated in DKO yBM cells. Restoration of WWOX in DKO-yBM cells reduced Myc protein levels. As a prototype target, we demonstrated upregulation of MCM7, a known Myc target, in DKO yBM relative to SKO yBM. Inhibition of MCM7 expression using Simvastatin resulted in reduced proliferation and tumor cell growth of DKO yBM cells. Our findings revealed BM-MSCs as a platform to study OS and Myc and its targets as WWOX effectors and early molecular events during osteosarcomagenesis.
2025-10-01 | GSE245606 | GEO
Project description:WWOX promotes osteosarcoma development via upregulation of Myc
| PRJNA1029051 | ENA
Project description:WWOX promotes osteosarcoma development via upregulation of Myc [ChIP-Seq]
| PRJNA1029058 | ENA
Project description:WWOX promotes osteosarcoma development via upregulation of Myc [RNA-Seq]
| PRJNA1029059 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2018-04-23 | GSE104823 | GEO
Project description:GINS2 is overexpressed in several cancers, but little is known about its role in osteosarcoma (OS). A series of in vivo and in vitro experiments were conducted to explore the role of GINS2 in OS. In this study, we demonstrated that GINS2 was found to be highly expressed in OS tissues and cell lines, which was associated with poor outcomes in OS patients. GINS2 knockdown hindered the growth and induced apoptosis in OS cell lines in vitro. Furthermore, GINS2 knockdown effectively inhibited the growth of a xenograft tumor in vivo. By using an Affymetrix gene chip and intelligent pathway analysis, it was demonstrated that the GINS2 knockdown could reduce the expression of several targeted genes and reduce the activity of the MYC signaling pathway. Mechanically, LC-MS, CoIP, and rescue experiments revealed that GINS2 promoted tumor progression through the STAT3/MYC axis in the OS. Moreover, GINS2 was associated with tumor immunity and may be a potential immunotherapeutic target for OS.
| S-EPMC9981285 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2016-10-07 | GSE84968 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2016-03-01 | E-GEOD-72898 | biostudies-arrayexpress