Format

Send to

Choose Destination
Anticancer Res. 2018 Feb;38(2):647-654.

Inhibition of Sirtuin 6 Induces Neuroblastoma Differentiation.

Author information

1
Robert H. Lurie Comprehensive Cancer Center, Northwestern University Medical Center, Chicago, IL, U.S.A.
2
Department of Pediatric Surgery, Vanderbilt University Medical Center, Nashville, TN, U.S.A.
3
Department of Pediatric Surgery, Vanderbilt University Medical Center, Nashville, TN, U.S.A. dai.chung@vanderbilt.edu.
4
Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN, U.S.A.

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.

KEYWORDS:

SIRT6; Sirtuins; differentiation; neuroblastoma; proliferation

PMID:
29374686
DOI:
10.21873/anticanres.12268
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center