The enhancer RNA ARIEL activates the oncogenic transcriptional program in T-cell acute lymphoblastic leukemia
| العنوان: | The enhancer RNA ARIEL activates the oncogenic transcriptional program in T-cell acute lymphoblastic leukemia |
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| المؤلفون: | Omer An, Daniel G. Tenen, Allen Eng Juh Yeoh, Zhenhua Li, Tze King Tan, Shi Hao Tan, Mei Chee Lim, Takaomi Sanda, Wei Zhong Leong, Melissa J. Fullwood, Phuong Cao Thi Ngoc, Fatima Carla Bertulfo |
| المساهمون: | School of Biological Sciences |
| المصدر: | Blood |
| بيانات النشر: | American Society of Hematology, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Transcription, Genetic, Carcinogenesis, T-Lymphocytes, Enhancer RNAs, Regulatory Sequences, Nucleic Acid, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Biochemistry, Mice, 0302 clinical medicine, Transcription (biology), hemic and lymphatic diseases, Adult T-cell Lymphoma, Promoter Regions, Genetic, T-Cell Acute Lymphocytic Leukemia Protein 1, Regulation of gene expression, Lymphoid Neoplasia, Gene Expression Regulation, Leukemic, Enhancer of Transcription, Biological sciences [Science], Hematology, Non-coding RNA, Cell biology, DNA-Binding Proteins, Enhancer Elements, Genetic, Gene Knockdown Techniques, 030220 oncology & carcinogenesis, Gene Targeting, Disease Progression, Chromatin Immunoprecipitation Sequencing, Heterografts, RNA, Long Noncoding, BLOOD Commentary, Protein Binding, Cell Survival, Immunology, Biology, Models, Biological, 03 medical and health sciences, Cell Line, Tumor, Animals, Humans, Enhancer, Transcription factor, Cell Proliferation, Binding Sites, RNA, Oncogenes, Cell Biology, Disease Models, Animal, 030104 developmental biology, Multiprotein Complexes, Transcription Factors, TAL1 |
| الوصف: | 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. NRF (Natl Research Foundation, S’pore) MOE (Min. of Education, S’pore) |
| تدمد: | 1528-0020 0006-4971 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cb3d82a06de68d1d0b7037a2008f05c7 https://doi.org/10.1182/blood.2018874503 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....cb3d82a06de68d1d0b7037a2008f05c7 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15280020 00064971 |
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