Inhibition of Sirtuin 6 Induces Neuroblastoma Differentiation.

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).

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.

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 p21CIP1 expression and G1 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.

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.

• Authors: Ha Yong Song, Eric J Rellinger, Seong-Hoon Park, Pritha Paul, Jingbo Qiao, Athanasios Vasilopoulos, Ozkan Ozden, David Gius, Dai H Chung
• Journal: Anticancer research (Anticancer Res) Vol. 38 Issue 2 Pg. 647-654 (02 2018) ISSN: 1791-7530 [Electronic] Greece
• PMID: 29374686 (Publication Type: Journal Article)
• Copyright: Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Chemical References

• RNA, Small Interfering
• Niacinamide
• Tretinoin
• SIRT6 protein, human
• Sirtuins

Topics

• Cell Differentiation (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Dose-Response Relationship, Drug
• Gene Knockdown Techniques
• Humans
• Neuroblastoma (drug therapy, metabolism, pathology)
• Niacinamide (pharmacology)
• RNA, Small Interfering (pharmacology)
• Sirtuins (antagonists & inhibitors, genetics)
• Tretinoin (administration & dosage, pharmacology)