Dysregulation of the transcription factor MYB plays a critical role in leukemia pathogenesis, progression, and prognosis; however, the detailed regulatory mechanisms of MYB remain unclear. Recently, we identified an enhancer long noncoding RNA (lncRNA) MY34UE-AS, which upregulates MYB expression. Here, we demonstrate that non-POU-domain-containing octamer binding protein (NONO) binds to MY34UE-AS through its RNA recognition motif 2 (RRM2) domain, thereby upregulating MYB expression and splicing. This interaction drives leukemia cell proliferation and migration. Our findings unveil a novel regulatory mechanism of MYB and propose the NONO-MY34UE-AS axis as a potential therapeutic target for leukemia. Impact statement Our study uncovers the NONO-MY34UE-AS-MYB regulatory axis in leukemia, revealing a new layer of MYB control. This mechanistic insight advances understanding of oncogenic transcription factor dysregulation and highlights potential therapeutic targets, offering new directions for leukemia research.
Shen et al. (Tue,) studied this question.