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

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.