核干细胞因子沉默通过自噬诱导人急性早幼粒细胞白血病NB4细胞分化并增强全反式维甲酸的作用。
Nucleostemin silencing induces differentiation and potentiates all-trans-retinoic acid effects in human acute promyelocytic leukemia NB4 cells via autophagy.
作者信息
Fakhimahmadi Aila, Nazmi Farinaz, Rahmati Marveh, Bonab Nazila Moghtaran, Hashemi Mehrdad, Moosavi Mohammad Amin
机构信息
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.
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.
出版信息
Leuk Res. 2017 Dec;63:15-21. doi: 10.1016/j.leukres.2017.10.007. Epub 2017 Oct 26.
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.
在此，我们报告称，通过特异性小干扰RNA（siNS）靶向最近发现的富含干细胞的基因核仁素（NS），可降低急性早幼粒细胞白血病（APL）NB4细胞的增殖速率，并诱导分化和自噬。此外，NS沉默可增强基于全反式维甲酸（ATRA）的分化疗法对NB4细胞的作用。自噬抑制剂3-甲基腺嘌呤和巴弗洛霉素可阻断NS靶向对分化的影响，表明NS与自噬之间存在新的功能联系，自噬是NB4细胞分化的重要调节因子。NS单独或与ATRA联合调节自噬和分化的能力，可能有助于拓宽白血病的治疗选择范围。
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