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|Title:||The enhancer RNA ARIEL activates the oncogenic transcriptional program in T-cell acute lymphoblastic leukemia||Authors:||Tan, Shi Hao
Leong, Wei Zhong
Ngoc, Phuong Cao Thi
Tan, Tze King
Bertulfo, Fatima Carla
Lim, Mei Chee
Yeoh, Allen Eng Juh
Tenen, Daniel G.
Fullwood, Melissa Jane
|Keywords:||Adult T-cell Lymphoma
Enhancer of Transcription
|Issue Date:||2019||Source:||Tan, S. H., Leong, W. Z., Ngoc, P. C. T., Tan, T. K., Bertulfo, F. C., Lim, M. C., . . . Sanda, T. (2019). The enhancer RNA ARIEL activates the oncogenic transcriptional program in T-cell acute lymphoblastic leukemia. Blood, 134(3), 239-251. doi:10.1182/blood.2018874503||Series/Report no.:||Blood||Abstract:||The oncogenic transcription factor TAL1 regulates the transcriptional program in T-ALL. ARID5B is one of the critical downstream targets of TAL1, which further activates the oncogenic regulatory circuit in T-ALL cells. Here, we elucidated the molecular functions of the noncoding RNA, ARID5B-inducing enhancer associated long noncoding RNA (ARIEL), in T-ALL pathogenesis. We demonstrated that ARIEL is specifically activated in TAL1+ T-ALL cases, and its expression is associated with ARID5B enhancer activity. ARIEL recruits mediator proteins to the ARID5B enhancer, promotes enhancer-promoter interactions, and activates the expression of ARID5B, thereby positively regulating the TAL1-induced transcriptional program and the MYC oncogene. The TAL1 complex coordinately regulates the expression of ARIEL. Knockdown of ARIEL inhibits cell growth and survival of T-ALL cells in culture and blocks disease progression in a murine xenograft model. Our results indicate that ARIEL plays an oncogenic role as an enhancer RNA in T-ALL.||URI:||https://hdl.handle.net/10356/104697
|DOI:||10.1182/blood.2018874503||Rights:||© 2019 The American Society of Hematology. All rights reserved.||Fulltext Permission:||none||Fulltext Availability:||No Fulltext|
|Appears in Collections:||SBS Journal Articles|
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