MOZ Forms an Autoregulatory Feedback Loop with miR-223 in AML and Monocyte/Macrophage Development

Monocytic leukemia zinc-finger protein (MOZ) has been found to form fusion proteins with many regulators in acute myeloid leukemia (AML). However, the molecular functions and underlying mechanism of MOZ in AML is not well understood. Here, clinical MOZ expression analysis combined with data integration from the TCGA and GEO databases indicated that a low level of MOZ was associated with poor prognosis. MOZ knockdown inhibited monocyte differentiation and increased resistance to chemotherapeutic drug-induced apoptosis in THP-1 or U937 cells. In addition, we found that genetic silencing of MOZ suppressed AP-1 and AKT activity in the context of lipopolysaccharide stimulation, resulting in diminished M1 activation of macrophages. We further showed that MOZ was a validated target of miR-223 and functioned as a repressor of miR-223 expression. Our study indicates that a molecular network involving MOZ and miR-223 contributes to the monocyte differentiation and polarization program, which is deregulated in AML.