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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 
Fullwood, Melissa J 
Tenen, Daniel G 
Sanda, Takaomi 
Issue Date: 10-May-2019
Citation: 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, Fullwood, Melissa J, Tenen, Daniel G, Sanda, Takaomi (2019-05-10). The enhancer RNA ARIEL activates the oncogenic transcriptional program in T-cell acute lymphoblastic leukemia.. Blood. ScholarBank@NUS Repository.
Abstract: The oncogenic transcription factor TAL1 regulates the transcriptional program in T-cell acute lymphoblastic leukemia (T-ALL). ARID5B is one of critical downstream targets of TAL1 which further activates the oncogenic regulatory circuit in T-ALL cells. Here, we elucidated the molecular functions of the non-coding RNA, ARID5B Inducing Enhancer Associated Long non-coding RNA (ARIEL), in T-ALL pathogenesis. We demonstrated that ARIEL is specifically activated in TAL1-positive 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.
Source Title: Blood
ISSN: 0006-4971
DOI: 10.1182/blood.2018874503
Appears in Collections:Staff Publications

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