A novel lncRNA SNHG29 regulates EP300- related histone acetylation modification and inhibits FLT3-ITD AML development

• Published in: Leukemia Vol. 37; no. 7; pp. 1421 - 1434
• Main Authors: Liu, Shan, Zhou, Jie, Ye, Xiangling, Chen, Danni, Chen, Weimin, Lin, Yaobin, Chen, Zhizhong, Chen, Biyun, Shang, Jin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.07.2023; Nature Publishing Group
• Subjects: 13/109; 13/31; 13/44; 13/51; 13/89; 14/32; 45/15; 45/77; 45/91; 59/5; 631/208; 631/67/1990/283/1897; 64/60; 82/58; Acetylation; Acute myeloid leukemia; Binding; Bone marrow; Cancer Research; Cell cycle; Cell proliferation; Critical Care Medicine; Cytarabine; Drug resistance; E1A-Associated p300 Protein - genetics; Epigenetics; fms-Like Tyrosine Kinase 3 - metabolism; Hematology; Histones; Histones - genetics; Histones - metabolism; Hospitals; Humans; Intensive; Internal Medicine; Kinases; Leukemia; Leukemia, Myeloid, Acute - pathology; Mass spectrometry; Medical prognosis; Medicine; Medicine & Public Health; Molecular modelling; Mutation; Non-coding RNA; Oncology; Protein-tyrosine kinase; Proteins; RNA polymerase; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Scientific imaging; Signal transduction; Stat5 protein; Therapeutic targets; Tumor suppressor genes; Tyrosine
• ISSN: 0887-6924; 1476-5551; 1476-5551
• DOI: 10.1038/s41375-023-01923-y

Internal tandem duplication (ITD) mutations within the FMS-like tyrosine kinase-3 (FLT3) occur in up to 25% of acute myeloid leukemia (AML) patients and indicate a very poor prognosis. The role of long noncoding RNAs (lncRNAs) in FLT3-ITD AML progression remains unexplored. We identified a novel lncRNA, SNHG29, whose expression is specifically regulated by the FLT3-STAT5 signaling pathway and is abnormally down-regulated in FLT3-ITD AML cell lines. SNHG29 functions as a tumor suppressor, significantly inhibiting FLT3-ITD AML cell proliferation and decreasing sensitivity to cytarabine in vitro and in vivo models. Mechanistically, we demonstrated that SNHG29’s molecular mechanism is EP300-binding dependent and identified the EP300-interacting region of SNHG29. SNHG29 modulates genome-wide EP300 genomic binding, affecting EP300-mediated histone modification and consequently influencing the expression of varies downstream AML-associated genes. Our study uncovers a novel molecular mechanism for SNHG29 in mediating FLT3-ITD AML biological behaviors through epigenetic modification, suggesting that SNHG29 could be a potential therapeutic target for FLT3-ITD AML.