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Article

Role of miR-34a-5p in Hematopoietic Progenitor Cells Proliferation and Fate Decision: Novel Insights into the Pathogenesis of Primary Myelofibrosis

1
Centre for Regenerative Medicine “Stefano Ferrari“, Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy
2
CRIMM, Center for Research and Innovation for Myeloproliferative Neoplasms, AOU Careggi and Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
3
Center for Genome Research, University of Modena and Reggio Emilia, 41125 Modena, Italy
*
Authors to whom correspondence should be addressed.
The AGIMM (AIRC Gruppo Italiano Malattie Mieloproliferative) investigators is provided in the Acknowledgments.
Academic Editor: Martin Pichler
Int. J. Mol. Sci. 2017, 18(1), 145; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms18010145
Received: 28 October 2016 / Revised: 5 January 2017 / Accepted: 6 January 2017 / Published: 13 January 2017
(This article belongs to the Collection Regulation by Non-Coding RNAs)
Primary Myelofibrosis (PMF) is a chronic Philadelphia-negative myeloproliferative neoplasm characterized by a skewed megakaryopoiesis and an overproduction of proinflammatory and profibrotic mediators that lead to the development of bone marrow (BM) fibrosis. Since we recently uncovered the upregulation of miR-34a-5p in PMF CD34+ hematopoietic progenitor cells (HPCs), in order to elucidate its role in PMF pathogenesis here we unravelled the effects of miR-34a-5p overexpression in HPCs. We showed that enforced expression of miR-34a-5p partially constrains proliferation and favours the megakaryocyte and monocyte/macrophage commitment of HPCs. Interestingly, we identified lymphoid enhancer-binding factor 1 (LEF1) and nuclear receptor subfamily 4, group A, member 2 (NR4A2) transcripts as miR-34a-5p-targets downregulated after miR-34a-5p overexpression in HPCs as well as in PMF CD34+ cells. Remarkably, the knockdown of NR4A2 in HPCs mimicked the antiproliferative effects of miR-34a-5p overexpression, while the silencing of LEF1 phenocopied the effects of miR-34a-5p overexpression on HPCs lineage choice, by favouring the megakaryocyte and monocyte/macrophage commitment. Collectively our data unravel the role of miR-34a-5p in HPCs fate decision and suggest that the increased expression of miR-34a-5p in PMF HPCs could be important for the skewing of megakaryopoiesis and the production of monocytes, that are key players in BM fibrosis in PMF patients. View Full-Text
Keywords: miR-34a-5p; nuclear receptor subfamily 4, group A, member 2 (NR4A2); lymphoid enhancer-binding factor 1 (LEF1); MYB; hematopoetic progenitor cells; hematopoietic differentiation; megakaryopoiesis; primary myelofibrosis; myeloproliferative neoplasms; macrophage miR-34a-5p; nuclear receptor subfamily 4, group A, member 2 (NR4A2); lymphoid enhancer-binding factor 1 (LEF1); MYB; hematopoetic progenitor cells; hematopoietic differentiation; megakaryopoiesis; primary myelofibrosis; myeloproliferative neoplasms; macrophage
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MDPI and ACS Style

Bianchi, E.; Ruberti, S.; Rontauroli, S.; Guglielmelli, P.; Salati, S.; Rossi, C.; Zini, R.; Tagliafico, E.; Vannucchi, A.M.; Manfredini, R. Role of miR-34a-5p in Hematopoietic Progenitor Cells Proliferation and Fate Decision: Novel Insights into the Pathogenesis of Primary Myelofibrosis. Int. J. Mol. Sci. 2017, 18, 145. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms18010145

AMA Style

Bianchi E, Ruberti S, Rontauroli S, Guglielmelli P, Salati S, Rossi C, Zini R, Tagliafico E, Vannucchi AM, Manfredini R. Role of miR-34a-5p in Hematopoietic Progenitor Cells Proliferation and Fate Decision: Novel Insights into the Pathogenesis of Primary Myelofibrosis. International Journal of Molecular Sciences. 2017; 18(1):145. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms18010145

Chicago/Turabian Style

Bianchi, Elisa, Samantha Ruberti, Sebastiano Rontauroli, Paola Guglielmelli, Simona Salati, Chiara Rossi, Roberta Zini, Enrico Tagliafico, Alessandro M. Vannucchi, and Rossella Manfredini. 2017. "Role of miR-34a-5p in Hematopoietic Progenitor Cells Proliferation and Fate Decision: Novel Insights into the Pathogenesis of Primary Myelofibrosis" International Journal of Molecular Sciences 18, no. 1: 145. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms18010145

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