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Targeted degradation of BRD9 reverses oncogenic gene expression in synovial sarcoma [ChIP-seq]

ABSTRACT: We used a CRISPR-based screening approach to identify functional vulnerabilities in pediatric sarcoma cell types, identifying BRD9 as an important dependency in synovial sarcoma cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE113228 | GEO | 2018/11/01

REPOSITORIES: GEO

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Targeted degradation of BRD9 reverses oncogenic gene expression in synovial sarcoma

Project description:This SuperSeries is composed of the SubSeries listed below.

2018-11-01 | GSE113229 | GEO

Gene expression analysis of synovial sarcoma, clinical samples

Project description:To identify molecular biomarkers that are useful for diagnosis and its targeting treatment, we analysed expression profile of synovial sarcoma tissue. In the present study, we studied gene expression profiles comparing 11 cases of synovial sarcoma.

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Project description:MicroRNAs (miRNAs) are non-coding small RNAs that function as an endogenous regulator of gene expression. Their dysregulation has been implicated in the development of several cancers. However, the status of miRNA in soft tissue sarcomas has not yet been thoroughly investigated. This study examined the global miRNA expression in synovial sarcoma and compared the results to those in another translocation-associated sarcoma, the Ewing family of tumors, and in normal skeletal muscle. The 3D-Gene miRNA microarray platform (Toray, Kamakura, Japan) and unsupervised hierarchical clustering revealed a distinct expression pattern of miRNAs in synovial sarcoma from Ewing tumors and skeletal muscle. Thirty-five of the more than 700 miRNAs analyzed were differentially expressed in synovial sarcomas in comparison to other tissue types. There were 21 significantly up-regulated miRNAs, including some miRNAs, such as let-7e, miR-99b and miR-125a-3p, clustered within the same chromosomal loci. Quantitative reverse transcription-polymerase chain reaction also demonstrated that these miRNAs were over-expressed in synovial sarcomas. The down-regulation of let-7e and miR-99b by anti-miR miRNA inhibitors resulted in the suppression of the proliferation of synovial sarcoma cells, and modulated the expression of their putative targets, HMGA2 and SMARCA5, suggesting that these molecules have a potential oncogenic role. The unique miRNA expression pattern including the over-expressed miRNA clusters in synovial sarcoma warrants further investigation in order to develop a better understanding of the oncogenic mechanisms and future therapeutic strategies for synovial sarcoma. Ten synovial sarcomas, five Ewing tumors and five normal skeletal muscle specimens are analyzed.

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Gene expression profile of poorly differentiated synovial sarcoma

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