MicroRNA 155 modulates megakaryopoiesis at progenitor and precursor level by targeting Ets‐1 and Meis1 transcription factors

• Published in: British journal of haematology Vol. 143; no. 4; pp. 570 - 580
• Main Authors: Romania, Paolo, Lulli, Valentina, Pelosi, Elvira, Biffoni, Mauro, Peschle, Cesare, Marziali, Giovanna
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.11.2008; Blackwell
• Subjects: Biological and medical sciences; Cell Differentiation - genetics; Cell Proliferation; Cells, Cultured; cord blood; Down-Regulation; Fetal Blood - cytology; haematopoietic progenitor cells; Hematologic and hematopoietic diseases; Hematopoietic Stem Cells - cytology; Homeodomain Proteins - genetics; Humans; K562 Cells; Medical sciences; megakaryocytes; Megakaryocytes - cytology; microRNAs; MicroRNAs - metabolism; MicroRNAs - physiology; Myeloid Ecotropic Viral Integration Site 1 Protein; Neoplasm Proteins - genetics; Proto-Oncogene Protein c-ets-1 - genetics; Proto-Oncogene Protein c-ets-1 - metabolism; Reverse Transcriptase Polymerase Chain Reaction - methods; RNA, Messenger - genetics; Thrombopoiesis - genetics; Thrombopoiesis - physiology; transcription factors; Transfection; microRNAs; Megakaryocytopoiesis; Transcription factor Ets; cord blood; RNA interference; megakaryocytes; Targeting; Hematology; transcription factors; Stem cell; Micro RNA; Hematopoietic cell; Megakaryocyte; Precursor; Blood; Gene silencing; Signal transduction; Umbilical cord; haematopoietic progenitor cells; Transcription factor
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/j.1365-2141.2008.07382.x

Summary MicroRNAs (miRNAs) control basic biological functions and are emerging as key regulators of haematopoiesis. This study focused on the functional role of MIRN155 on megakaryocytic (MK) differentiation of human cord blood CD34+ haematopoietic progenitor cells (HPCs). MIRN155, abundantly expressed in early HPCs, decreases sharply during MK differentiation. Functional studies showed that enforced expression of MIRN155 impairs proliferation and differentiation of MK cells. Furthermore, HPCs transfected with MIRN155 showed a significant reduction of their MK clonogenic capacity, suggesting that down‐modulation of this miRNA favours MK progenitor differentiation. Consistent with this observation, MIRN155 down‐regulates, by directly binding to their 3′‐UTR, the expression of Ets‐1 and Meis1, two transcription factors with well‐known functions in MK cells. These results show that the decline of MIRN155 is required for MK proliferation and differentiation at progenitors and precursors level and indicate that sustained expression of MIRN155 inhibits megakaryopoiesis.