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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
An, Omer
Li, Zhenhua
Yeoh, Allen Eng Juh
Tenen, Daniel G.
Sanda, Takaomi
Fullwood, Melissa Jane
Keywords: Adult T-cell Lymphoma
Enhancer of Transcription
Science::Biological sciences
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.
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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