NONO regulates monocyte-macrophage lineage differentiation through a potential PI3K/AKT-dependent mechanism

Non-POU domain containing octamer binding protein (NONO) is a multifunctional nuclear protein which plays important roles in regulating nuclear processes such as transcription and splicing. We aimed to delineate the effects and the underlying mechanisms of NONO on monocyte-macrophage lineage differentiation. By depolying a phorbol 12-myristate 13-acetate (PMA)-induced THP-1 cell differentiation model and a macrophage colony-stimulating factor (M-CSF)-induced mouse bone marrow cell differentiation model, we examined the expression pattern and the effects of NONO during monocyte-macrophage lineage differentiation. The research revealed that the expression of NONO protein progressively decreased during the M-CSF-induced differentiation of mouse bone marrow cells into macrophages and the PMA-induced differentiation of THP-1 human monocytic leukemia cells into macrophages. The monocyte-macrophage lineage differentiation process was enhanced in Nono gene knockout (Nono K.O.) mouse bone marrow cells as well as NONO knockdown (NONO K.D.) THP-1 cells. The study also found that reduced NONO expression enhanced the AKT phosphorylation during macrophage lineage differentiation. At the same time, the PI3K inhibitor suppressed THP-1 cell differentiation into macrophages and attenuated the AKT phosphorylation activation by PMA and NONO knockdown during PMA-induced differentiation of THP-1 cells into macrophages. These results suggested an important role of NONO in regulating monocyte-macrophage lineage differentiation and this process was mediated, at least partially, through PI3K/AKT signaling pathway.