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miRNA let-7c promotes granulocytic differentiation in acute myeloid leukemia

Oncogene volume 32, pages 3648–3654 (2013)Cite this article

Abstract

MicroRNAs (miRNAs), small non-coding RNAs that regulate gene expression post-transcriptionally, are involved in many complex cellular processes. Several miRNAs are differentially expressed in hematopoietic tissues and play important roles in normal differentiation, but, when aberrantly regulated, contribute to the abnormal proliferation and differentiation of leukemic cells. Recently, we reported that a small subset of miRNAs is differentially expressed in acute promyelocytic leukemia (APL) blasts and is modulated by treatment with all-trans-retinoic acid (ATRA). In particular, PML/RARα-positive blasts from APL patients display lower levels of miRNA let-7c, a member of the let-7 family, than normal promyelocytes and its expression increases after ATRA treatment. In this study, we investigated the effects of let-7c in acute myeloid leukemia (AML) cells. We found that ectopic expression of let-7c promotes granulocytic differentiation of AML cell lines and primary blasts. Moreover, we identified PBX2, a well-known homeodomain protein whose aberrant expression enhances HoxA9-dependent leukemogenesis, as a novel let-7c target that may contribute to the AML phenotype. Together, these studies raise the possibility that perturbation of the let-7c-PBX2 pathway may have a therapeutic value in AML.

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Acknowledgements

We thank Dr Alessandro Fatica from ‘Sapienza’ University in Rome for a kind gift of lentiviral vector pRRLSIN-cPPT-PGK-GFP-WPRE and Dr Gianluca Bossi for kindly providing information on lentiviral utilization; Alessandra Boe for technical assistance for cell sorting and FACS analysis. We also acknowledge Dr Silvia Bacchetti for helpful comments on the manuscript. Associazione Italiana Leucemie (AIL) and Ministry of Health, Ricerca oncologica-Project of integrated program to MGR. G Piaggio was supported, in part, by Associazione Italiana Ricerca sul Cancro (AIRC). B Calabretta was supported, in part, by NCI grant CA95111. A Pelosi and S Careccia are PhD students University of Rome ‘Sapienza’. A Pelosi is a recipient of a fellowship from AIRC. S Careccia is a recipient of the fellowship AIL ‘Alberto Landi’.

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Author notes

  1. P Romania

    Present address: 10Current address: Department of Pediatric Hematology/Oncology, IRCCS, Ospedale Pediatrico Bambino Gesù, Rome, Italy.,

  2. A Pelosi and S Careccia: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Experimental Oncology, Laboratory of Molecular Oncogenesis, Regina Elena National Cancer Institute, Rome, Italy

    A Pelosi, S Careccia, G Piaggio & M G Rizzo

  2. Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy

    V Lulli, P Romania, G Marziali & U Testa

  3. Department of Biopathology, Tor Vergata University, Rome, Italy

    S Lavorgna & F Lo-Coco

  4. Laboratory of Neuro-Oncohematology, Santa Lucia Foundation, Rome, Italy

    S Lavorgna & F Lo-Coco

  5. Department of Medical Oncology, Hematology Division, Regina Elena National Cancer Institute, Rome, Italy

    M C Petti

  6. Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA

    B Calabretta

  7. Department of Internal Medicine, Sapienza University of Rome, Rome, Italy

    M Levrero

  8. Laboratory of Gene Expression, Fondazione Andrea Cesalpino, Rome, Italy

    M Levrero

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Correspondence to M G Rizzo.

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Pelosi, A., Careccia, S., Lulli, V. et al. miRNA let-7c promotes granulocytic differentiation in acute myeloid leukemia. Oncogene 32, 3648–3654 (2013). https://doi.org/10.1038/onc.2012.398

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