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Histone Deacetylase inhibitor, LBH589, has antitumor effects on undifferentiated pleomorphic sarcoma cells via the downregulation of FOSL1

ABSTRACT: Histone Deacetylase inhibitor, LBH589, has antitumor effects on undifferentiated pleomorphic sarcoma cells via the downregulation of FOSL1

PROVIDER: PRJNA412176 | ENA |

REPOSITORIES: ENA

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Histone Deacetylase inhibitor, LBH589, has antitumor effects on undifferentiated pleomorphic sarcoma cells via the downregulation of FOSL1

Project description:Background Epigenetic mutations are involved in oncogenesis and therefore their regulator Histone deacetylaces (HDACs) can be a therapeutic target. In this study, we investigated the anticancer effect and mechanism of pan-HDAC inhibitor, LBH589, against undifferentiated pleomorphic sarcoma (UPS). Method To elucidate the molecular target, we performed RNA microarray for UPS cells after treated LBH589. Data were validated by RT-PCR and Westernblot. Result We found that LBH589 decrease the expression of Fos-like 1 (FOSL1) gene in four UPS cell lines. Knockdown of FOSL1 by RNA interference inhibited cell proliferation and conversely, overexpression increased cell proliferative capacity. Furthermore, we showed that knockdown of FOSL1 cause elevation of p21 expression in UPS cells. Conclusion FOSL1 codes the FRA-1 protein and forms activator protein-1 (AP-1) complexes in collaboration with members of the JUN family to drive gene transcription. FOSL1 is overexpressed in several malignant tumors and considered to be a poor prognostic factor. In this study, we showed that the antitumor effect by HDAC inhibitor is partly due to down regulation of FOSL1.

2017-09-27 | GSE104256 | GEO

Undifferentiated Pleomorphic Sarcoma Model

Project description:Analysis of undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma-like tumors from LSL-KrasG12D, p53Fl/Fl mouse model of soft tissue sarcoma.

2009-11-21 | GSE16779 | GEO

Undifferentiated Pleomorphic Sarcoma Model Using Tumors from BrafCa

Project description:Analysis of undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma like tumors from BrafCa, p53Fl/Fl mouse model of soft tissue sarcoma

2014-12-01 | GSE20049 | GEO

Undifferentiated Pleomorphic Sarcoma Model

Project description:Analysis of undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma-like tumors from LSL-KrasG12D, p53Fl/Fl mouse model of soft tissue sarcoma. Murine soft tissue sarcomas (n = 17) were compared to normal muscle (n = 4). Tumors were isolated surgically from soft tissue sarcomas generated by conditional Kras and p53 alleles. Tumors were induced using an adenovirus expressing Cre recombinase. Normal muscle samples were isolated from mice of the same genotype without tumor induction.

2010-03-03 | E-GEOD-16779 | biostudies-arrayexpress

Transcriptomic analysis of 162 myxofibrosarcomas and undifferentiated pleomorphic sarcomas

Project description:The global gene expression profiles of 162 myxofibrosarcomas and undifferentiated pleomorphic sarcomas were studied by RNA-sequencing. The profiles were compared with clinical and genomic features. 21 soft tissue tumors of other histotypes were used as out-group.

2024-09-30 | E-MTAB-13947 | biostudies-arrayexpress

Segment files from SNP array analysis of 145 myxofibrosarcoma and undifferentiated pleomorphic sarcoma

Project description:Genomic profiling of myxofibrosarcoma and undifferentiated pleomorphic sarcomas was done to correlate genomic profiles and signatures with outcome and transcriptomic features.

2024-09-30 | E-MTAB-13948 | biostudies-arrayexpress

Copy number alteration profiling of myxofibrosarcoma and undifferentiated pleomorphic sarcoma

Project description:We used array-based comparative genomic hybridization to identify copy number alterations in the TP53 and RB1 tumor suppressor genes in 64 myxofibrosarcoma and 30 undifferentiated pleomorphic sarcoma primary untreated tumor samples, and found that 68% of tumor samples had shallow or deep deletions in one or both genes.

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Gene expression profiling in leiomyosarcomas and undifferentiated pleomorphic sarcomas: SRC as a new diagnostic marker

Project description:Transcriptional profiling of leiomyosarcomas (LMS) and undifferentiated pleomorphic sarcomas (UPS) aiming to identify molecular biomarkers. Data were validated using RT-qPCR. To assess the relevance of the gene signature, a meta-analysis was performed using five published studies. SRC protein immunolabeling was performed for 38 UPS and 52 LMS.

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Shared prognostic markers in undifferentiated pleomorphic sarcoma and leiomyosarcoma of the extremities

Project description:Soft tissue sarcoma diagnostics and prognostics are challenging, particularly in highly malignant and pleomorphic subtypes such as undifferentiated pleomorphic sarcoma (UPS) and leiomyosarcoma (LMS). We applied 32K BAC-arrays and gene expression profiling to 18 extremity soft tissue LMS and 31 extremity soft tissue UPS with the aim to identify molecular subtype signatures and genomic prognostic markers. Both the gains/losses and gene expression signatures revealed striking similarities between UPS and LMS, which were indistinguishable using unsupervised hierarchical cluster analysis and significance analysis for microarrays. Gene expression analysis revealed just 9 genes, among them Tropomyosin beta, that were differentially expressed. Loss of 4q31 (encompassing the SMAD1 locus), loss of 18q22 and tumor necrosis were identified as independent predictors of metastasis in multivariate stepwise Cox regression analysis. Combined analysis applying loss of 4q31 and 18q22 and presence of necrosis improved the area under receiver operating characteristic curve for metastasis prediction from 0.64 to 0.86. The extensive genetic similarities between extremity soft tissue UPS and LMS suggest a shared lineage of these STS subtypes and the new and independent genetic prognosticators identified hold promise for refined prognostic determination in high-grade, genetically complex STS. Genomic DNA was extracted from a total of 49 samples, 31 Undifferentiated pleomorphic Sarcomas and 18 Leiomyosarcomas. The DNA was labeled using Bioprime array CGH labeling kit (Invitrogen). Promega pooled male DNA was used as reference. Labeled DNA was hybridized onto BAC arrays containing ~32 000 BAC clones printed in singlets. BAC arrays were produced at the SWEGENE DNA Microarray Facility at Lund University.

2010-10-08 | E-GEOD-13775 | biostudies-arrayexpress

Single cell RNA-sequencing of undifferentiated pleomorphic sarcomas and leiomyosarcomas.

Project description:Single cell RNA-sequencing of undifferentiated pleomorphic sarcomas and leiomyosarcomas.

| PRJNA875907 | ENA