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.
Footnotes
↵* These Authors contributed equally to this study.
This article is freely accessible online.
Conflicts of Interest
The Authors declare no potential conflicts of interest in regard to this study.
Funding
This work was supported by grants from the National Institutes of Health (R01 DK61470) and Rally Foundation for Cancer Research.
- Received September 29, 2017.
- Revision received December 4, 2017.
- Accepted December 5, 2017.
- Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved
