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Nucleostemin Silencing Induces Differentiation and Potentiates All-Trans-Retinoic Acid Effects in Human Acute Promyelocytic Leukemia Nb4 Cells Via Autophagy Publisher Pubmed



Fakhimahmadi A1, 2 ; Nazmi F1, 3 ; Rahmati M4, 5 ; Bonab NM3 ; Hashemi M2 ; Moosavi MA1
Authors
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Authors Affiliations
  1. 1. Department of Molecular Medicine, National Institute of Genetic Engineering and Biotechnology, P.O. Box: 14965/161, Tehran, Iran
  2. 2. Islamic Azad University Tehran Medical Branch, Tehran, Iran
  3. 3. Department of Biology, Faculty of Natural Science, University of Tabriz, P.O. Box 51666-16471, Tabriz, Iran
  4. 4. Cancer Biology Research Center, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

Source: Leukemia Research Published:2017


Abstract

Here, we report that targeting Nucleostemin (NS), a recently discovered stem cells-enriched gene, by a specific small interference RNA (siNS), decreases the rate of proliferation of acute promyelocytic leukemia (APL) NB4 cells and induces differentiation and autophagy. In addition, NS silencing promotes the effects of all-trans-retinoic acid (ATRA)-based differentiation therapy in NB4 cells. Autophagy inhibitors 3-methyladenine and bafilomycin block the effect of NS targeting on differentiation, indicating a new functional link between NS and autophagy as an important regulator of differentiation in NB4 cells. The capability of NS in modulating autophagy and differentiation, alone or in combination with ATRA, may help to broaden the range of treatment options available to treat leukemia. © 2017 Elsevier Ltd
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