Nucleostemin silencing induces differentiation and potentiates all-trans-retinoic acid effects in human acute promyelocytic leukemia NB4 cells via autophagy

Aila Fakhimahmadi; Farinaz Nazmi; Marveh Rahmati; Nazila Moghtaran Bonab; Mehrdad Hashemi; Mohammad Amin Moosavi

doi:10.1016/j.leukres.2017.10.007

Nucleostemin silencing induces differentiation and potentiates all-trans-retinoic acid effects in human acute promyelocytic leukemia NB4 cells via autophagy

Leuk Res. 2017 Dec:63:15-21. doi: 10.1016/j.leukres.2017.10.007. Epub 2017 Oct 26.

Authors

Aila Fakhimahmadi¹, Farinaz Nazmi², Marveh Rahmati³, Nazila Moghtaran Bonab⁴, Mehrdad Hashemi⁵, Mohammad Amin Moosavi⁶

Affiliations

¹ Department of Molecular Medicine, National Institute of Genetic Engineering and Biotechnology, P.O. Box:14965/161, Tehran, Iran; Islamic Azad University Tehran Medical Branch, Tehran, Iran.
² Department of Molecular Medicine, National Institute of Genetic Engineering and Biotechnology, P.O. Box:14965/161, Tehran, Iran; Department of Biology, Faculty of Natural Science, University of Tabriz, P.O. Box 51666-16471, Tabriz, Iran.
³ Cancer Biology Research Center, Tehran University of Medical Sciences, Tehran, Iran; Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
⁴ Department of Biology, Faculty of Natural Science, University of Tabriz, P.O. Box 51666-16471, Tabriz, Iran.
⁵ Islamic Azad University Tehran Medical Branch, Tehran, Iran.
⁶ Department of Molecular Medicine, National Institute of Genetic Engineering and Biotechnology, P.O. Box:14965/161, Tehran, Iran. Electronic address: a-moosavi@nigeb.ac.ir.

PMID: 29096331
DOI: 10.1016/j.leukres.2017.10.007

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.

Keywords: Acute promyelocytic leukemia; All-trans-retinoic acid; Autophagy; Differentiation; Nucleostemin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / pharmacology
Apoptosis / drug effects
Autophagy / drug effects*
Cell Differentiation / drug effects*
Cell Proliferation / drug effects
GTP-Binding Proteins / antagonists & inhibitors*
GTP-Binding Proteins / genetics
Gene Expression Regulation, Neoplastic / drug effects*
Gene Silencing*
Humans
Leukemia, Promyelocytic, Acute / drug therapy
Leukemia, Promyelocytic, Acute / genetics
Leukemia, Promyelocytic, Acute / pathology*
Nuclear Proteins / antagonists & inhibitors*
Nuclear Proteins / genetics
RNA, Small Interfering / genetics
Tretinoin / pharmacology*
Tumor Cells, Cultured

Substances

Antineoplastic Agents
GNL3 protein, human
Nuclear Proteins
RNA, Small Interfering
Tretinoin
GTP-Binding Proteins