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Inhibition of Sirtuin 6 Induces Neuroblastoma Differentiation.

Authors :: Song HY
Rellinger EJ
Park SH
Paul P
Qiao J
Vasilopoulos A
Ozden O
Gius D
Chung DH
Source :: Anticancer research [Anticancer Res] 2018 Feb; Vol. 38 (2), pp. 647-654.
Publication Year :: 2018
Abstract: Background/aim: Sirtuins (SIRTs) play crucial roles in various signaling pathways that modulate differentiation and proliferation. We sought to elucidate the role of SIRTs in differentiation and proliferation of human neuroblastoma (NB).<br />Materials and Methods: NB cells were treated with nicotinamide (NAM), a non-specific SIRT inhibitor, SIRT-targeted short hairpin RNAs, and retinoic acid to assess cell growth and differentiation.<br />Results: SIRTs are involved in proliferation and differentiation using NAM in BE(2)-C cells. Specifically, SIRT6 knockdown in BE(2)-C cells reduced cell proliferation, induced neurite extension, corresponding with induction of p21 <superscript>CIP1</superscript> expression and G <subscript>1</subscript> cell-cycle arrest. These effects were rescued by forced re-overexpression of SIRT6. SIRT6 expression was reduced in differentiated human NB sections, and RA-induced differentiation in BE(2)-C cells.<br />Conclusion: SIRTs have important oncogenic properties in NB beyond its established functions in aging and genome stability. SIRT6 may represent a novel target for developing future therapeutics for the treatment of aggressive NBs.<br /> (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)