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LIN28B underlies the pathogenesis and therapeutic sensitivity of a subclass of Ewing sarcoma

ABSTRACT: LIN28B underlies the pathogenesis and therapeutic sensitivity of a subclass of Ewing sarcoma

PROVIDER: PRJNA505813 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8200100.fastq.gz	Fastqsanger.gz
	SRR8200091.fastq.gz	Fastqsanger.gz
	SRR8200101.fastq.gz	Fastqsanger.gz
	SRR8200092.fastq.gz	Fastqsanger.gz
	SRR8200102.fastq.gz	Fastqsanger.gz

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LIN28B underlies the pathogenesis of a subclass of Ewing sarcoma

Project description:LIN28B underlies the pathogenesis of a subclass of Ewing sarcoma

| PRJNA566347 | ENA

LIN28B underlies the pathogenesis of a subclass of Ewing sarcoma

Project description:Ewing sarcoma (EwS) is associated with poor prognosis despite current multimodal therapy. Targeting of EWS-FLI-1, the fusion protein responsible for its pathogenesis, and its principal downstream targets has not yet produced satisfactory therapeutic options, fuelling the search for alternative approaches. Here, we show that the oncofoetal RNA-binding protein Lin28B regulates the stability of EWS-FLI-1 mRNA in about 10% of EwS. Lin28B depletion in these tumours leads to a decrease in expression of EWS-FLI-1 and its direct transcriptional network, abrogating EwS cell self-renewal and tumorigenicity. Moreover, pharmacological inhibition of Lin28B mimics the effect of Lin28B depletion, suggesting that Lin28B sustains the emergence of a subset of EwS in which it also serves as an effective therapeutic target.

2020-04-30 | GSE137703 | GEO

LIN28B underlies the pathogenesis and therapeutic sensitivity of a subclass of Ewing sarcoma

Project description:Ewing sarcoma (EwS) is a pediatric bone malignancy associated with high mortality despite aggressive multimodal therapy. Targeting EWS-FLI-1, the fusion protein responsible for EwS pathogenesis, or its principal downstream target gene products have not produced effective therapeutic options, fuelling the quest for alternative approaches. Here, we show that the oncofoetal RNA-binding protein Lin28B is expressed in a subset of EwS in which it directly binds and safeguards EWS-FLI-1 transcripts. Depletion and pharmacologic inhibition of Lin28B in primary patient-derived EwS cultures led not only to a decrease in EWS-FLI-1 expression but also to the deconstruction of its direct transcriptional network, abrogating EwS cell self-renewal and tumorigenicity. Our observations demonstrate that Lin28B provides indispensable support for EWS-FLI-1 to sustain the emergence of a EwS subset in which it also constitutes a promising therapeutic target.

2020-04-30 | GSE122632 | GEO

Carrier Subclass

Project description:Carrier Subclass

| PRJNA1031099 | ENA

Ewing Sarcoma

Project description:This SuperSeries is composed of the following subset Series: GSE36857: Goldengate Methylation analysis: Ewing Sarcoma GSE36858: 5- AZA treatment of EWS cell lines Refer to individual Series

2012-09-01 | E-GEOD-36859 | biostudies-arrayexpress

Transcription profiling of human Ewing sarcoma samples and EWS-FLI-1 inhibited Ewing sarcoma cell lines

Project description:The cellular origin of Ewing tumor (ET), a tumor of bone or soft tissues characterized by specific fusions between EWS and ETS genes, is highly debated. Through gene expression analysis comparing ETs with a variety of normal tissues, we show that the profiles of different EWS-FLI1-silenced Ewing cell lines converge toward that of mesenchymal stem cells (MSC). Moreover, upon EWS-FLI1 silencing, two different Ewing cell lines can differentiate along the adipogenic lineage when incubated in appropriate differentiation cocktails. In addition, Ewing cells can also differentiate along the osteogenic lineage upon long-term inhibition of EWS-FLI1. These in silico and experimental data strongly suggest that the inhibition of EWS-FLI1 may allow Ewing cells to recover the phenotype of their MSC progenitor. Experiment Overall Design: Ewing tumors and EWS-FLI-1 inhibited cell lines were profiled on Affymetrix U133A (GPL96) arrays.

2008-06-15 | E-GEOD-7007 | biostudies-arrayexpress

RUNX3 Facilitates Growth of Ewing Sarcoma Cells

Project description:Ewing sarcoma is an aggressive pediatric small round cell tumor that predominantly occurs in bone. Approximately 85% of Ewing sarcomas harbor the EWS/FLI fusion protein, which arises from a chromosomal translocation, t(11:22)(q24:q12). EWS/FLI interacts with numerous lineage-essential transcription factors to maintain mesenchymal progenitors in an undifferentiated state. We previously showed that EWS/FLI binds the osteogenic transcription factor RUNX2 and prevents osteoblast differentiation. In this study, we investigated the role of another Runt-domain protein, RUNX3, in Ewing sarcoma. RUNX3 participates in mesenchymal-derived bone formation and is a context dependent tumor suppressor and oncogene. RUNX3 was detected in all Ewing sarcoma cells examined, whereas RUNX2 was detected in only 73% of specimens. Like RUNX2, RUNX3 binds to EWS/FLI via its Runt domain. EWS/FLI prevented RUNX3 from activating the transcription of a RUNX-responsive reporter, p6OSE2. Stable suppression of RUNX3 expression in the Ewing sarcoma cell line A673 delayed colony growth in anchorage independent soft agar assays and reversed expression of EWS/FLI-responsive genes. These results demonstrate an important role for RUNX3 in Ewing sarcoma. RNA-seq to compare transcriptiome of control A673 ewing sarcoma cells stably expression a non-target or RUNX3 shRNA

2014-05-01 | E-GEOD-56900 | biostudies-arrayexpress

Expression profile of Ewing sarcoma and osteosarcoma

Project description:The expression profile of primary pediatric Ewing sarcoma (ES) and osteosarcoma (OS) were analyzed. 8 Ewing sarcoma patient samples (TUM-ES0XXX) and 10 osteosarcoma patient samples (TUM-OS0XXX) were analyzed.

2016-07-05 | E-GEOD-73166 | biostudies-arrayexpress

Ewing sarcoma cell lines

Project description:Ewing sarcoma cell lines

| PRJNA690225 | ENA

Methylation profile of ewing sarcoma cell lines

Project description:Study of promoter methylation of ewing sarcoma cell lines and mesenchymal stem cell from ewing sarcoma patients and healthy donors

2018-10-24 | GSE118872 | GEO

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