Please use this identifier to cite or link to this item: https://doi.org/10.1093/nar/gky1207
Title: Super-enhancer-associated MEIS1 promotes transcriptional dysregulation in Ewing sarcoma in co-operation with EWS-FLI1
Authors: Lin, L.
Huang, M.
Shi, X.
Mayakonda, A. 
Hu, K.
Jiang, Y.-Y. 
Guo, X.
Chen, L.
Pang, B.
Doan, N.
Said, J.W.
Xie, J.
Gery, S.
Cheng, X.
Lin, Z.
Li, J.
Berman, B.P.
Yin, D.
Lin, D.-C.
Koeffler, H.P. 
Issue Date: 2019
Publisher: Oxford University Press
Citation: Lin, L., Huang, M., Shi, X., Mayakonda, A., Hu, K., Jiang, Y.-Y., Guo, X., Chen, L., Pang, B., Doan, N., Said, J.W., Xie, J., Gery, S., Cheng, X., Lin, Z., Li, J., Berman, B.P., Yin, D., Lin, D.-C., Koeffler, H.P. (2019). Super-enhancer-associated MEIS1 promotes transcriptional dysregulation in Ewing sarcoma in co-operation with EWS-FLI1. Nucleic Acids Research 47 (3) : 1255-12567. ScholarBank@NUS Repository. https://doi.org/10.1093/nar/gky1207
Rights: Attribution-NonCommercial 4.0 International
Abstract: As the second most common malignant bone tumor in children and adolescents, Ewing sarcoma is initiated and exacerbated by a chimeric oncoprotein, most commonly, EWS-FLI1. In this study, we apply epigenomic analysis to characterize the transcription dysregulation in this cancer, focusing on the investigation of super-enhancer and its associated transcriptional regulatory mechanisms. We demonstrate that super-enhancer-associated transcripts are significantly enriched in EWS-FLI1 target genes, contribute to the aberrant transcriptional network of the disease, and mediate the exceptional sensitivity of Ewing sarcoma to transcriptional inhibition. Through integrative analysis, we identify MEIS1 as a super-enhancer-driven oncogene, which co-operates with EWS-FLI1 in transcriptional regulation, and plays a key pro-survival role in Ewing sarcoma. Moreover, APCDD1, another super-enhancer associated gene, acting as a downstream target of both MEIS1 and EWS-FLI1, is also characterized as a novel tumor-promoting factor in this malignancy. These data delineate super-enhancer-mediated transcriptional deregulation in Ewing sarcoma, and uncover numerous candidate oncogenes which can be exploited for further understanding of the molecular pathogenesis for this disease. © The Author(s) 2018.
Source Title: Nucleic Acids Research
URI: https://scholarbank.nus.edu.sg/handle/10635/213709
ISSN: 0305-1048
DOI: 10.1093/nar/gky1207
Rights: Attribution-NonCommercial 4.0 International
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