A restricted signature of miRNAs distinguishes APL blasts from normal promyelocytes.
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.
Careccia
S
S
Laboratory of Molecular Oncogenesis, Department of Experimental Oncology, Regina Elena Cancer Institute, Rome 00158, Italy.
Mainardi
S
S
Pelosi
A
A
Gurtner
A
A
Diverio
D
D
Riccioni
R
R
Testa
U
U
Pelosi
E
E
Piaggio
G
G
Sacchi
A
A
Lavorgna
S
S
Lo-Coco
F
F
Blandino
G
G
Levrero
M
M
Rizzo
M G
MG
D042381:Granulocyte Precursor Cells / Q000473:pathology; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000032:analysis* / Q000235:genetics
D035683:MicroRNAs