2. Academic Validation
  3. NONO regulates monocyte-macrophage lineage differentiation through a potential PI3K/AKT-dependent mechanism

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

  • Differentiation. 2025 Sep-Oct:145:100901. doi: 10.1016/j.diff.2025.100901.
Xiu-Rong Wei 1,  Dan Hu 1,  Zi-Jiang Yang 1,  Lv-Bin Yan 2,  Guang-Yu Xu 1,  Rui-Gang Zhang 3,  Xiu-Juan Zhang 4
Affiliations

Affiliations

  • 1 Department of Physiology, Basic Medical School, Guangdong Medical University, Zhanjiang, China.
  • 2 Library, Guangdong Medical University, Zhanjiang, China.
  • 3 Department of Physiology, Basic Medical School, Guangdong Medical University, Zhanjiang, China. Electronic address: rgzhang@gdmu.edu.cn.
  • 4 Department of Physiology, Basic Medical School, Guangdong Medical University, Zhanjiang, China. Electronic address: xiujuanzhang@gdmu.edu.cn.
PMID: 40857758 DOI: 10.1016/j.diff.2025.100901
Abstract

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.

Keywords

Differentiation; Macrophage; NONO; PI3K/AKT.

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