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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
45
pubmed:dateCreated
2009-11-12
pubmed:abstractText
MicroRNAs (miRNAs) are small non-coding RNAs involved in the regulation of critical cell processes such as apoptosis, cell proliferation and differentiation. A small set of miRNAs is differentially expressed in hematopoietic cells and seemingly has an important role in granulopoiesis and lineage differentiation. In this study, we analysed, using a quantitative real-time PCR approach, the expression of 12 granulocytic differentiation signature miRNAs in a cohort of acute promyelocytic leukemia (APL) patients. We found nine miRNAs overexpressed and three miRNAs (miR-107, -342 and let-7c) downregulated in APL blasts as compared with normal promyelocytes differentiated in vitro from CD34+ progenitors. Patients successfully treated with all-trans-retinoic acid (ATRA) and chemotherapy showed downregulation of miR-181b and upregulation of miR-15b, -16, -107, -223, -342 and let-7c. We further investigated whether the APL-associated oncogene, promyelocytic leukemia gene (PML)/retinoic acid receptor alpha (RARalpha), might be involved in the transcriptional repression of miR-107, -342 and let-7c. We found that PML/RARalpha binds the regulatory sequences of the intragenic miR-342 and let-7c. In addition, we observed, in response to ATRA, the release of PML/RARalpha paralleled by their transcriptional activation, together with their host genes, EVL and C21orf34alpha. In conclusion, we show that a small subset of miRNAs is differentially expressed in APL and modulated by ATRA-based treatment.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1476-5594
pubmed:author
pubmed:issnType
Electronic
pubmed:day
12
pubmed:volume
28
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4034-40
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
A restricted signature of miRNAs distinguishes APL blasts from normal promyelocytes.
pubmed:affiliation
Laboratory of Molecular Oncogenesis, Department of Experimental Oncology, Regina Elena Cancer Institute, Rome 00158, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't