Expression profiling of histone deacetylase (HDAC) family member genes in human synovial sarcoma cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE126152 | GEO | 2019/02/06
REPOSITORIES: GEO
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Project description:Histone deacetylase (HDAC) inhibition has been shown in previous studies to disrupt the synovial sarcoma oncoprotein complex, resulting in apoptosis. To understand the molecular effects of HDAC inhibition, RNA-Seq transcriptome analysis was undertaken in six human synovial sarcoma cell lines. HDAC inhibition induced pathways of cell cycle arrest, neuronal differentiation and response to oxygen-containing species, effects also observed in other cancers treated with this class of drugs. More specific to synovial sarcoma, polycomb-group targets were reactivated including tumor suppressor CDKN2A, and pro-apoptotic transcriptional patterns were induced. Functional analyses revealed that ROS-mediated FOXO activation and pro-apoptotic factors BIK, BIM and BMF were important to apoptosis induction following HDAC-inhibition in synovial sarcoma
| EGAS00001002637 | EGA
Project description:Expression profiling of histone deacetylase (HDAC) family member genes in human synovial sarcoma cells
| PRJNA521158 | ENA
Project description:Expression of the SS18/SYT-SSX fusion protein is believed to underlie the pathogenesis of synovial sarcoma (SS). Recent evidence suggests that deregulation of the Wnt pathway may play an important role in SS but the mechanisms whereby SS18-SSX might affect Wnt signaling remain to be elucidated. Here, we show that SS18/SSX tightly regulates the elevated expression of the key Wnt target AXIN2 in primary SS. SS18-SSX is shown to interact with TCF/LEF, TLE and HDAC but not β -catenin in vivo and to induce Wnt target gene expression by forming a complex containing promoter-bound TCF/LEF and HDAC but lacking β -catenin. Our observations provide a tumor-specific mechanistic basis for Wnt target gene induction in SS that can occur in the absence of Wnt ligand stimulation.
2016-02-23 | GSE78159 | GEO
Project description:Expression of the SS18/SYT-SSX fusion protein is believed to underlie the pathogenesis of synovial sarcoma (SS). Recent evidence suggests that deregulation of the Wnt pathway may play an important role in SS but the mechanisms whereby SS18-SSX might affect Wnt signaling remain to be elucidated. Here, we show that SS18/SSX tightly regulates the elevated expression of the key Wnt target AXIN2 in primary SS. SS18-SSX is shown to interact with TCF/LEF, TLE and HDAC but not β -catenin in vivo and to induce Wnt target gene expression by forming a complex containing promoter-bound TCF/LEF and HDAC but lacking β -catenin. Our observations provide a tumor-specific mechanistic basis for Wnt target gene induction in SS that can occur in the absence of Wnt ligand stimulation. SS18SSX expressing C3H cells vs control: no replicates. WNT-stimulated C3H cells vs controls: 3 replicates per condition
2016-02-23 | E-GEOD-78159 | biostudies-arrayexpress
Project description:We systematically explored the transcriptome of 10 synovial sarcoma (SS) patients. We detected a large number of upregulated and downregulated genes in SS compared to normal tissues, which were mainly involved in cell cycle, metabolic and P53 signaling pathways. Moreover, we identified a multitude of differentially alternative spliced genes, indicating that the deregulation of alternative splicing could be one of main factors contribute to the tumorigenesis of SS. A set of tumor-specific gene fusion pairs were identified in SS. We also detected dozens of differentially expressed circRNAs and their parental genes were enriched in muscle related biological process. The interaction network constructed based on circRNAs, miRNAs and corresponding target genes showed that the differentially expressed circRNAs in SS have the potential to regulate the expression of a number of SS related genes. Collectively, we systematically investigated the abnormal expression profile of SS and gain insights into the molecular mechanism from different views of transcriptome expression changes.
2022-02-01 | GSE144190 | GEO
Project description:Poorly differentiated type synovial sarcoma (PDSS) is a variant of synovial sarcoma characterized by predominantly round or short-spindled cells. Although accumulating evidence from clinicopathological studies suggests a strong association between this variant of synovial sarcoma and poor prognosis, little has been reported on the molecular basis of PDSS. To gain insight into the mechanism(s) that underlie the emergence of PDSS, we analyzed the gene expression profiles of 34 synovial sarcoma clinical samples, including 5 cases of PDSS, using an oligonucleotide microarray. In an unsupervised analysis, the 34 samples fell into 3 groups that correlated highly with histological subtype, namely, monophasic, biphasic, and poorly differentiated types. PDSS was characterized by down-regulation of genes associated with neuronal and skeletal development and cell adhesion, and up-regulation of genes on a specific chromosomal locus, 8q21.11. This locus-specific transcriptional activation in PDSS was confirmed by reverse transcriptase (RT)-PCR analysis of 9 additional synovial sarcoma samples. Our results indicate that PDSS tumors constitute a distinct genetic group based on expression profiles. 34 SYT-SSX fusion transcript-positive SS samples, consisting of 21 MSS, 8 BSS and 5 PDSS cases, were analyzed using an oligonucleotide microarray using a GeneChip Human Genome U133 plus 2.0 array (Affymetrix).
2010-09-01 | E-GEOD-20196 | biostudies-arrayexpress
Project description:comparative genome hybridisation of Hdac1/2 cKO lymphomas and matched normal tissue Histone deacetylases (HDACs) are epigenetic erasers of lysine-acetyl marks. Inhibition of HDACs using small molecule inhibitors (HDACi) is a potential strategy in the treatment of various diseases and is approved for treating hematological malignancies. Harnessing the therapeutic potential of HDACi requires knowledge of HDAC-function in vivo. Here, we generated a thymocyte-specific gradient of HDAC-activity using compound conditional knockout mice for Hdac1 and Hdac2. Unexpectedly, gradual loss of HDAC-activity engendered a dosage dependent accumulation of immature thymocytes and correlated with the incidence and latency of monoclonal lymphoblastic thymic lymphomas. Strikingly, complete ablation of Hdac1 and Hdac2 abrogated lymphomagenesis due to a block in early thymic development. Genomic, biochemical and functional analyses of pre-leukemic thymocytes and tumors revealed a critical role for Hdac1/Hdac2-governed HDAC-activity in regulating a p53-dependent barrier to constrain Myc-overexpressing thymocytes from progressing into lymphomas by regulating Myc-collaborating genes. One Myc-collaborating and p53-suppressing gene, Jdp2, was derepressed in an Hdac1/2-dependent manner and critical for the survival of Jdp2-overexpressing lymphoma cells. Although reduced HDAC-activity facilitates oncogenic transformation in normal cells, resulting tumor cells remain highly dependent on HDAC-activity, indicating that a critical level of Hdac1 and Hdac2 governed HDAC-activity is required for tumor maintenance. genomic DNA from LckCre+;Hdac1/2 cKO lymphomas and matched normal genomic DNA was hybridized onto a Nimblegen whole genome array
2013-01-11 | E-GEOD-43407 | biostudies-arrayexpress
Project description:Transcriptome comparisons by RNAseq of genetically engineered mouse models of synovial sarcoma, expressing SS18-SSX1 or SS18-SSX2 and having homozygous conditional genetic silencing of Pten or wildtype Pten.
2016-11-03 | GSE81476 | GEO
Project description:Translocation-related sarcomas (TRSs) harbor an oncogenic fusion gene generated by chromosome translocation and account for approximately one-third of all sarcomas; however, effective targeted therapies have not yet been established. We previously reported that a pan-PI3K inhibitor, ZSTK474, was suggested to be effective for sarcomas in a phase I clinical trial, and demonstrated its efficacy in preclinical model, particularly in cell lines from synovial sarcomas (SS), Ewing’s sarcomas (ES) and alveolar rhabdomyosarcomas (ARMS), all of which harbor chromosomal translocation. Actually, ZSTK474 selectively induced apoptosis in these types of sarcoma cell lines, but the precise mechanism of apoptosis induction remained unclear. Here, we performed transcriptional analyses in SS cell lines including Aska-SS, SYO-1, Yamato-SS and Fuji treated with or without ZSTK474. Gene set enrichment analyses (GSEA) and Gene ontology (GO) analysis revealed that SS cell lines treated with ZSTK474 significantly reduced signatures of PI3K signaling. In addition, upon treatment with ZSTK474, the expression of apoptosis and cell cycle related genes was significantly changed. Importantly, PI3K inhibitors triggered induction of PUMA and BIM, resulting in loss of mitochondrial membrane potential, and the expression knockdown of these genes by RNA interference efficiently suppressed the apoptosis, suggesting their functional involvement in the apoptosis progression. In contrast, TRS-derived cell lines/patient-derived cells from alveolar soft part sarcoma (ASPS), CIC-DUX4 sarcoma and dermatofibrosarcoma protuberans failed to undergo apoptosis nor induce PUMA and BIM expression, as well as cell lines derived from non-TRSs and carcinomas. These results indicate that PI3K inhibitors selectively induce apoptosis in selective TRSs such as ES and SS via the induction of PUMA and BIM and subsequent loss of mitochondrial membrane potential, which would be a proof of concept for PI3K-targeted therapy especially for such TRS patients.
2023-03-08 | GSE221131 | GEO
Project description:Synovial sarcoma (SS) is defined by the hallmark SS18-SSX fusion oncoprotein, which renders BAF complexes aberrant in two manners: gain of SSX to the SS18 subunit and concomitant loss of BAF47 subunit assembly. Here we demonstrate that SS18-SSX globally hijacks BAF complexes on chromatin to activate a SS transcriptional signature we define using primary tumors and cell lines. Specifically, SS18-SSX retargets BAF complexes from enhancers to broad polycomb domains to oppose PRC2-mediated repression and activate bivalent genes. Upon suppression of SS18-SSX, reassembly of BAF47 restores enhancer activation, but is not required for proliferative arrest. These results establish a global hijacking mechanism for SS18-SSX on chromatin, and define the distinct contributions of two concurrent BAF complex perturbations.
2018-05-31 | GSE114487 | GEO