MicroRNA fingerprints during human megakaryocytopoiesis.
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.
Department of Molecular Virology, Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210, USA.
Ramiro
R
Garzon
Flavia
F
Pichiorri
Tiziana
T
Palumbo
Rodolfo
R
Iuliano
Amelia
A
Cimmino
Rami
R
Aqeilan
Stefano
S
Volinia
Darshna
D
Bhatt
Hansjuerg
H
Alder
Guido
G
Marcucci
George A
GA
Calin
Chang-Gong
CG
Liu
Clara D
CD
Bloomfield
Michael
M
Andreeff
Carlo M
CM
Croce
D018952:Antigens, CD34 / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D002454:Cell Differentiation; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics; D006801:Humans; D051258:MafB Transcription Factor / Q000378:metabolism; D008533:Megakaryocytes / Q000166:cytology* / Q000378:metabolism*; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D009690:Nucleic Acid Conformation; D009710:Nucleotide Mapping; D015513:Oncogene Proteins / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*
D018952:Antigens, CD34; D018398:Homeodomain Proteins; C490407:MAFB protein, human; D051258:MafB Transcription Factor; D035683:MicroRNAs; D015513:Oncogene Proteins