MicroRNA Fingerprints during Human Megakaryocytopoiesis

• Published in: Proceedings of the National Academy of Sciences - PNAS 2006-03, Vol.103 (13), p.5078-5083
• Main Authors: Garzon, Ramiro, Pichiorri, Flavia, Palumbo, Tiziana, Iuliano, Rodolfo, Cimmino, Amelia, Aqeilan, Rami, Volinia, Stefano, Bhatt, Darshna, Alder, Hansjuerg, Marcucci, Guido, Calin, George A., Liu, Chang-Gong, Bloomfield, Clara D., Andreeff, Michael, Croce, Carlo M.
• Format: Article
• Language: English
• Subjects: Antigens, CD34 - genetics; Antigens, CD34 - metabolism; Base Sequence; Biological Sciences; Cell Differentiation; Cell lines; Cells, Cultured; Cellular biology; Gene Expression Regulation; Genes; Homeodomain Proteins - chemistry; Homeodomain Proteins - genetics; Humans; K562 cells; Leukemia; MafB Transcription Factor - metabolism; Medicine; Megakaryocytes; Megakaryocytes - cytology; Megakaryocytes - metabolism; MicroRNA; MicroRNAs - chemistry; MicroRNAs - genetics; Nucleic Acid Conformation; Nucleotide Mapping; Oncogene Proteins - metabolism; Progenitor cells; Proteins; Reverse transcriptase polymerase chain reaction; Ribonucleic acid; RNA; Stem cells; Stem Cells - cytology; Stem Cells - metabolism
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0600587103

microRNAs are a highly conserved class of noncoding RNAs with important regulatory functions in proliferation, apoptosis, development, and differentiation. To discover novel regulatory pathways during megakaryocytic differentiation, we performed microRNA expression profiling of in vitro-differentiated megakaryocytes derived from$CD34^+$hematopoietic progenitors. The main finding was down-regulation of miR-10a, miR-126, miR-106, miR-10b, miR-17 and miR-20. Hypothetically, the down-regulation of microRNAs unblocks target genes involved in differentiation. We confirmed in vitro and in vivo that miR-130a targets the transcription factor MAFB, which is involved in the activation of the GPIIB promoter, a key protein for platelet physiology. In addition, we found that miR-10a expression in differentiated megakaryocytes is inverse to that of HOXA1, and we showed that HOXA1 is a direct target of miR-10a. Finally, we compared the microRNA expression of megakaryoblastic leukemic cell lines with that of in vitro differentiated megakaryocytes and$CD34^+$progenitors. This analysis revealed up-regulation of miR-101, miR-126, miR-99a, miR-135, and miR-20. Our data delineate the expression of microRNAs during megakaryocytopoiesis and suggest a regulatory role of microRNAs in this process by targeting megakaryocytic transcription factors.