In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 74, No. 20_Supplement ( 2014-10-15), p. A75-A75
Kurzfassung:
Ewing Sarcoma is an aggressive pediatric bone and soft tissue malignancy driven by transcription factor oncogenic fusions, of which EWS/Fli1 is the most common. Our studies of the role of microRNAs in EWS/Fli1-driven oncogenesis have uncovered a new tumor-promoting pathway in Ewing Sarcoma. Specifically, we have found that EWS/Fli1 downregulates miR-22, which in turn results in increased expression of the H3K9 histone demethylase, and miR-22 target, KDM3A. Overexpression of miR-22 and stable depletion of KDM3A each results in impaired clonogenic and anchorage-independent growth of Ewing Sarcoma cells. KDM3A depletion further results in impaired tumorigenesis in a xenograft model, upregulation of the repressive H3K9 methyl histone mark, and diminished expression of multiple oncogenes in Ewing Sarcoma. Our studies thus identify a new, potentially targetable, tumor-promoting pathway in Ewing Sarcoma, involving modulation of H3K9 histone methylation downstream of EWS/Fli1. Citation Format: Janet K. Parrish, Marybeth Sechler, Paul Jedlicka. A new, microRNA-regulated, epigenetic tumor-promoting pathway in Ewing sarcoma. [abstract]. In: Proceedings of the AACR Special Conference on Pediatric Cancer at the Crossroads: Translating Discovery into Improved Outcomes; Nov 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;74(20 Suppl):Abstract nr A75.
Materialart:
Online-Ressource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.PEDCAN-A75
Sprache:
Englisch
Verlag:
American Association for Cancer Research (AACR)
Publikationsdatum:
2014
ZDB Id:
2036785-5
ZDB Id:
1432-1
ZDB Id:
410466-3
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