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EWS-FLI1 and HOXD13 control tumor cell plasticity in Ewing sarcoma [RNA-seq]

ABSTRACT: Posterior homeobox D genes, in particular HOXD13, are over-expressed by Ewing sarcoma, a tumor driven by the oncogenic fusion protein EWS-FLI1. Here, we have found that EWS-FLI1 maintains HOXD13 expression through a GGAA microsatellite enhancer in the developmental posterior HOXD regulatory domain. Activation of this enhancer is EWS-FLI1 dependent and epigenomic silencing of this region leads to loss of HOXD13 expression in Ewing sarcoma cells, but not in unrelated cells. To determine the function of HOXD13 activation in Ewing sarcoma we performed nascent RNA sequencing or RNA sequencing upon HOXD13 knockdown.

ORGANISM(S): Homo sapiens

PROVIDER: GSE148494 | GEO | 2022/06/28

REPOSITORIES: GEO

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EWS-FLI1 and HOXD13 control tumor cell plasticity in Ewing sarcoma [CITE-seq]

Project description:Posterior homeobox D genes, in particular HOXD13, are over-expressed by Ewing sarcoma, a tumor driven by the oncogenic fusion protein EWS-FLI1. Here, we have found that EWS-FLI1 maintains HOXD13 expression through a GGAA microsatellite enhancer in the developmental posterior HOXD regulatory domain. Activation of this enhancer is EWS-FLI1 dependent and epigenomic silencing of this region leads to loss of HOXD13 expression in Ewing sarcoma cells, but not in unrelated cells. To determine the function of HOXD13 activation in Ewing sarcoma we performed nascent RNA sequencing upon HOXD13 knockdown. We identified NT5E as a target induced by HOXD13. NT5E encodes for the cell surface marker CD73, so we used CITE-seq to profile these cells.

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EWS-FLI1 and HOXD13 control tumor cell plasticity in Ewing sarcoma [CUT&RUN]

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EWS-FLI1 and HOXD13 control tumor cell plasticity in Ewing sarcoma

Project description:EWS-FLI1 and HOXD13 control tumor cell plasticity in Ewing sarcoma

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USP1 expression driven by EWS-FLI1 transcription factor stabilizes Survivin and promotes Ewing sarcoma cell survival

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