A restricted signature of miRNAs distinguishes APL blasts from normal promyelocytes

S. Careccia, S. Mainardi, A. Pelosi, A. Gurtner, D. Diverio, R. Riccioni, U. Testa, E. Pelosi, G. Piaggio, A. Sacchi, S. Lavorgna, F. Lo-Coco, G. Blandino, M. Levrero, M. G. Rizzo

Research output: Contribution to journalArticlepeer-review

Abstract

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 α (RARα), might be involved in the transcriptional repression of miR-107,-342 and let-7c. We found that PML/RARα binds the regulatory sequences of the intragenic miR-342 and let-7c. In addition, we observed, in response to ATRA, the release of PML/RARα paralleled by their transcriptional activation, together with their host genes, EVL and C21orf34α. In conclusion, we show that a small subset of miRNAs is differentially expressed in APL and modulated by ATRA-based treatment.

Original languageEnglish
Pages (from-to)4034-4040
Number of pages7
JournalOncogene
Volume28
Issue number45
DOIs
Publication statusPublished - Nov 2009

Keywords

  • Acute promyelocytic leukemia
  • MicroRNAs
  • PML/RARa

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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