A novel miR-200b-3p/p38IP pair regulates monocyte/macrophage differentiation
Open Access
- 26 January 2016
- journal article
- Published by Springer Science and Business Media LLC in Cell Discovery
- Vol. 2 (1), 15043
- https://doi.org/10.1038/celldisc.2015.43
Abstract
Monocyte/macrophage differentiation represents a major branch of hematopoiesis and is a central event in the immune response, but the molecular mechanisms underlying are not fully delineated. Here we show that p38 mitogen-activated protein kinase (MAPK) interacting protein (p38IP) is downregulated during monocyte/macrophage differentiation in vitro. Overexpression of p38IP halted monocyte/macrophage differentiation, whereas forward knockdown of p38IP by RNA interference induced G1/S arrest and promoted monocyte differentiation into macrophages and the maturation of macrophages as well. Moreover, we found that miR-200b-3p was upregulated during monocyte/macrophage differentiation and mediated the downregulation of p38IP by binding to the 3′ untranslated terminal region of p38IP mRNA. Overexpression of a miR-200b-3p mimic resembled the effect of p38IP knockdown, whereas a miR-200b-3p inhibitor blocked monocyte/macrophage differentiation by enhancing p38IP expression. Further western blotting analysis revealed that p38IP downregulation enhanced the activity of p38 MAPK and the subsequent accumulation of cyclin-dependent kinase inhibitor p21, thus promoting G1/S arrest and monocyte/macrophage differentiation. Moreover, the decline of GCN5 acetyltransferase caused by p38IP downregulation was required but was not sufficient for monocyte/macrophage differentiation. This study demonstrated a new role for p38IP and a novel miR-200b-3p/p38IP pair in the regulation of monocyte/macrophage differentiation.Keywords
This publication has 72 references indexed in Scilit:
- MiR-181 mediates cell differentiation by interrupting the Lin28 and let-7 feedback circuitCell Death & Differentiation, 2011
- Regulation of erythroid differentiation by miR-376a and its targetsCell Research, 2011
- miR-200c is upregulated by oxidative stress and induces endothelial cell apoptosis and senescence via ZEB1 inhibitionCell Death & Differentiation, 2011
- p53 spreads out further: suppression of EMT and stemness by activating miR-200c expressionCell Research, 2011
- Myc-Nick: A Cytoplasmic Cleavage Product of Myc that Promotes α-Tubulin Acetylation and Cell DifferentiationCell, 2010
- Coordinated regulation of autophagy by p38α MAPK through mAtg9 and p38IPThe EMBO Journal, 2009
- Downregulation of miRNA-200c Links Breast Cancer Stem Cells with Normal Stem CellsCell, 2009
- The Epithelial-Mesenchymal Transition Generates Cells with Properties of Stem CellsCell, 2008
- Glucocorticoid-stimulated preadipocyte differentiation is mediated through acetylation of C/EBPβ by GCN5Proceedings of the National Academy of Sciences of the United States of America, 2007
- Activation and signaling of the p38 MAP kinase pathwayCell Research, 2005