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Leukemia. 2017 Nov;31(11):2315-2325. doi: 10.1038/leu.2017.64. Epub 2017 Feb 20.

miR-194-5p/BCLAF1 deregulation in AML tumorigenesis.

Author information

1
Institute of Genetics and Biophysics, CNR, Naples, Italy.
2
Department of Biochemistry, Biophysics and General Pathology, Universitá degli studi della Campania-Luigi Vanvitelli, Naples, Italy.
3
Faculty of Science, Department of Molecular Biology, Radboud Institute for Molecular Life Sciences, Radboud University, Nijmegen, The Netherlands.
4
Centre for Research in Molecular Medicine, The University of Lahore, Lahore, Pakistan.
5
Umberto I Hospital, Salerno, Italy.
6
Department of Experimental Oncology, European Institute of Oncology, Milan, Italy.

Abstract

Deregulation of epigenetic mechanisms, including microRNA, contributes to leukemogenesis and drug resistance by interfering with cancer-specific molecular pathways. Here, we show that the balance between miR-194-5p and its newly discovered target BCL2-associated transcription factor 1 (BCLAF1) regulates differentiation and survival of normal hematopoietic progenitors. In acute myeloid leukemias this balance is perturbed, locking cells into an immature, potentially 'immortal' state. Enhanced expression of miR-194-5p by treatment with the histone deacetylase inhibitor SAHA or by exogenous miR-194-5p expression re-sensitizes cells to differentiation and apoptosis by inducing BCLAF1 to shuttle between nucleus and cytosol. miR-194-5p/BCLAF1 balance was found commonly deregulated in 60 primary acute myeloid leukemia patients and was largely restored by ex vivo SAHA treatment. Our findings link treatment responsiveness to re-instatement of miR-194-5p/BCLAF1 balance.

PMID:
28216661
PMCID:
PMC5668498
DOI:
10.1038/leu.2017.64
[Indexed for MEDLINE]
Free PMC Article

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