Rosa A, Ballarino M, Sorrentino A, Sthandier O, De Angelis FG, Marchioni M et al.. The interplay between the master transcription factor PU.1 and miR-424 regulates human monocyte/macrophage differentiation. Proc Natl Acad Sci USA 104: 19849-19854

Institute Pasteur Cenci-Bolognetti, Department of Genetics and Molecular Biology, Institute of Molecular Biology and Pathology, and Department of Cellular Biotechnologies and Hematology, University of Rome "La Sapienza", Rome, Italy.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 01/2008; 104(50):19849-54. DOI: 10.1073/pnas.0706963104
Source: PubMed


We describe a pathway by which the master transcription factor PU.1 regulates human monocyte/macrophage differentiation. This includes miR-424 and the transcriptional factor NFI-A. We show that PU.1 and these two components are interlinked in a finely tuned temporal and regulatory circuitry: PU.1 activates the transcription of miR-424, and this up-regulation is involved in stimulating monocyte differentiation through miR-424-dependent translational repression of NFI-A. In turn, the decrease in NFI-A levels is important for the activation of differentiation-specific genes such as M-CSFr. In line with these data, both RNAi against NFI-A and ectopic expression of miR-424 in precursor cells enhance monocytic differentiation, whereas the ectopic expression of NFI-A has an opposite effect. The interplay among these three components was demonstrated in myeloid cell lines as well as in human CD34+ differentiation. These data point to the important role of miR-424 and NFI-A in controlling the monocyte/macrophage differentiation program.

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Available from: Alessandro Rosa, May 20, 2014
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    • "The role of miR-424 has been investigated in several types of physiological and pathological conditions, which revealed the diverse function of miR-424 in different situations. It was reported that miR-424 was implicated in maintaining the physiology of vascular remodeling and angiogenesis24, remodeling of the epithelium in the mammary gland25, protecting against permanent focal cerebral ischemia injury26, promoting differentiation of monocytes27 and skeletal muscle-derived progenitor cells28. Recently, an interesting study showed that miR-424 was involved in APLN-dependent miRNA-FGF signaling axis needed for the maintenance of pulmonary vascular homeostasis29. "
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    • "Recent evidence suggests that microRNAs (miRNAs or miRs) are important regulators of normal hematopoietic differentiation [8-13]. Transcription factors such as PU.1 regulate a number of miRNAs, and correspondingly, miRNAs also regulate transcription factor expression in normal hematopoiesis [11,12,14,15]. For example, miR-223 and the transcription factors CEPBA, PU.1, NFI-A and E2F2 contribute to a regulatory circuit that controls normal granulopoiesis [16,17]. "
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