Journal
BLOOD
Volume 134, Issue 3, Pages 239-251Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood.2018874503
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Funding
- National Research Foundation (NRF) Singapore
- Singapore Ministry of Education (MOE) under its Research Centres of Excellence initiative
- NRF under its Competitive Research Programme [NRF-NRFF2013-02, NRF-NRFF2012-054]
- RNA Biology Center at Cancer Science Institute (CSI) Singapore, National University of Singapore (NUS), Singapore MOE's Research Fund Tier 3 [MOE2014-T3-1-006]
- Singapore Translational Research (STaR) Investigator Award
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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.
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