The enhancer RNA ARIEL activates the oncogenic transcriptional program in T-cell acute lymphoblastic leukemia

• Main 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
• Other Authors: School of Biological Sciences
• Format: Article
• Language: English
• Published: 2019
• Subjects: Adult T-cell Lymphoma; Enhancer of Transcription; Science::Biological sciences
• Online Access: https://hdl.handle.net/10356/104697; http://hdl.handle.net/10220/50301
• Institution: Nanyang Technological University

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.