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| Content Provider | MDPI |
|---|---|
| Author | Bianchi, Elisa Ruberti, Samantha Rontauroli, Sebastiano Guglielmelli, Paola Salati, Simona Rossi, Chiara Zini, Roberta Tagliafico, Enrico Vannucchi, Alessandro Manfredini, Rossella |
| Abstract | 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. |
| File Size | 9357312 |
| File Format | |
| e-ISSN | 14220067 |
| DOI | 10.3390/ijms18010145 |
| Journal | International Journal of Molecular Sciences |
| Issue Number | 1 |
| Volume Number | 18 |
| Language | English |
| Publisher Date | 2017-01-13 |
| Access Restriction | Open |
| Subject Keyword | 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 |
| Content Type | Text |
| Resource Type | Article |
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