MicroRNA fingerprints during human megakaryocytopoiesis

Ramiro Garzon, Flavia Pichiorri, Tiziana Palumbo, Rodolfo Iuliano, Amelia Cimmino, Rami Aqeilan, Stefano Volinia, Darshna Bhatt, Hansjuerg Alder, Guido Marcucci, George A. Calin, Chang Gong Liu, Clara D. Bloomfield, Michael Andreeff, Carlo M. Croce*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

397 Scopus citations

Abstract

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.

Original languageAmerican English
Pages (from-to)5078-5083
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number13
DOIs
StatePublished - 28 Mar 2006
Externally publishedYes

Keywords

  • Hematopoiesis
  • Leukemia

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