Abstract A31: The long noncoding RNA lnc277 mediates a repressive gene signature in Ewing's sarcoma

• Published in: Cancer research (Chicago, Ill.) Vol. 74; no. 20_Supplement; p. A31
• Main Authors: Marques, Michelle, Simpson, David, Chen, Ron, Vaka, Dedeepya, Breese, Marcus, Brunner, Allayne, West, Rob, Sweet-Cordero, Alejandro
• Format: Journal Article
• Language: English
• Published: 15.10.2014
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.PEDCAN-A31

Abstract Ewing's sarcoma is a highly aggressive tumor characterized by a translocation between members of the FET family of RNA binding proteins and one of several ETS transcription factors, with the most common translocation being EWS-FLI1. Like many oncogenic translocations, EWS-FLI1 leads to changes in gene expression through mechanisms that are not completely understood. We performed RNA sequencing analysis on human mesenchymal progenitor cells (MPCs) expressing EWS-FLI1, which are thought to be the cell of origin of Ewing's sarcoma. This analysis identified lnc277 as a previously uncharacterized long non-coding RNA upregulated by EWS-FLI1 in MPCs. Expression of lnc277 in Ewing's sarcoma cell lines requires EWS-FLI1. In addition, inhibiting the expression of lnc277 diminished the ability of Ewing's sarcoma cell lines to proliferate and form soft agar colonies. Using RNA sequencing and shRNA knockdown, we defined the transcriptional changes induced by EWS-FLI1 and lnc277. This analysis revealed that both EWS-FLI1 and lnc277 repress far more genes that they induce and that a large fraction of EWS-FLI1 repressed targets are also modulated by lnc277. Thus, lnc277 is an oncogenic long non-coding RNA downstream of EWS-FLI1 that facilitates the formation of Ewing's sarcoma via the repression of target genes. Citation Format: Michelle Marques, David Simpson, Ron Chen, Dedeepya Vaka, Marcus Breese, Allayne Brunner, Rob West, Alejandro Sweet-Cordero. The long noncoding RNA lnc277 mediates a repressive gene signature in Ewing's 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 A31.