Abstract
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.
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