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.
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Acknowledgements
We thank Dr WH Miller Jr for kindly providing the NB4 sub-clone MR2 and Dr I Sperduti for his help on statistical analysis. This work was supported by grants from Associazione Italiana per la Ricerca sul Cancro (AIRC), Ministero della Salute-Italy and European Community (Eu Active p53 Consortium).
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Careccia, S., Mainardi, S., Pelosi, A. et al. A restricted signature of miRNAs distinguishes APL blasts from normal promyelocytes. Oncogene 28, 4034–4040 (2009). https://doi.org/10.1038/onc.2009.255
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DOI: https://doi.org/10.1038/onc.2009.255
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