Inhibition of sirtuin 6 induces neuroblastoma differentiation

Ha Yong Song; Eric J. Rellinger; Seong Hoon Park; Pritha Paul; Jingbo Qiao; Athanasios Vasilopoulos; Ozkan Ozden; David Gius; Dai H. Chung

doi:10.21873/anticanres.12268

Inhibition of sirtuin 6 induces neuroblastoma differentiation

Ha Yong Song, Eric J. Rellinger, Seong Hoon Park, Pritha Paul, Jingbo Qiao, Athanasios Vasilopoulos, Ozkan Ozden, David Gius, Dai H. Chung

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

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 p21^CIP1 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.

Original language	English
Pages (from-to)	647-654
Number of pages	8
Journal	Anticancer Research
Volume	38
Issue number	2
DOIs	https://doi.org/10.21873/anticanres.12268
State	Published - Feb 2018

Bibliographical note

Funding Information:
The Authors thank Karen Martin for her aid in manuscript preparation. Flow Cytometry experiments were performed in the VMC Flow Cytometry Shared Resource. The VMC Flow Cytometry Shared Resource is supported by the Vanderbilt Ingram Cancer Center (P30CA68485) and the Vanderbilt Digestive Disease Research Center (DK058404).

Funding Information:
This work was supported by grants from the National Institutes of Health (R01 DK61470) and Rally Foundation for Cancer Research.

Funding Information:
This work was supported by grants from the National Institutes of Health (R01 DK61470) and Rally Foundation for Cancer Research. The Authors thank Karen Martin for her aid in manuscript preparation. Flow Cytometry experiments were performed in the VMC Flow Cytometry Shared Resource. The VMC Flow Cytometry Shared Resource is supported by the Vanderbilt Ingram Cancer Center (P30CA68485) and the Vanderbilt Digestive Disease Research Center (DK058404).

Publisher Copyright:
© 2018 International Institute of Anticancer Research. All Rights Reserved.

Keywords

Differentiation
Neuroblastoma
Proliferation
SIRT6
Sirtuins

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.21873/anticanres.12268

Cite this

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title = "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.",

keywords = "Differentiation, Neuroblastoma, Proliferation, SIRT6, Sirtuins",

author = "Song, {Ha Yong} and Rellinger, {Eric J.} and Park, {Seong Hoon} and Pritha Paul and Jingbo Qiao and Athanasios Vasilopoulos and Ozkan Ozden and David Gius and Chung, {Dai H.}",

note = "Funding Information: The Authors thank Karen Martin for her aid in manuscript preparation. Flow Cytometry experiments were performed in the VMC Flow Cytometry Shared Resource. The VMC Flow Cytometry Shared Resource is supported by the Vanderbilt Ingram Cancer Center (P30CA68485) and the Vanderbilt Digestive Disease Research Center (DK058404). Funding Information: This work was supported by grants from the National Institutes of Health (R01 DK61470) and Rally Foundation for Cancer Research. Funding Information: This work was supported by grants from the National Institutes of Health (R01 DK61470) and Rally Foundation for Cancer Research. The Authors thank Karen Martin for her aid in manuscript preparation. Flow Cytometry experiments were performed in the VMC Flow Cytometry Shared Resource. The VMC Flow Cytometry Shared Resource is supported by the Vanderbilt Ingram Cancer Center (P30CA68485) and the Vanderbilt Digestive Disease Research Center (DK058404). Publisher Copyright: {\textcopyright} 2018 International Institute of Anticancer Research. All Rights Reserved.",

year = "2018",

month = feb,

doi = "10.21873/anticanres.12268",

language = "English",

volume = "38",

pages = "647--654",

number = "2",

}

TY - JOUR

T1 - Inhibition of sirtuin 6 induces neuroblastoma differentiation

AU - Song, Ha Yong

AU - Rellinger, Eric J.

AU - Park, Seong Hoon

AU - Paul, Pritha

AU - Qiao, Jingbo

AU - Vasilopoulos, Athanasios

AU - Ozden, Ozkan

AU - Gius, David

AU - Chung, Dai H.

N1 - Funding Information: The Authors thank Karen Martin for her aid in manuscript preparation. Flow Cytometry experiments were performed in the VMC Flow Cytometry Shared Resource. The VMC Flow Cytometry Shared Resource is supported by the Vanderbilt Ingram Cancer Center (P30CA68485) and the Vanderbilt Digestive Disease Research Center (DK058404). Funding Information: This work was supported by grants from the National Institutes of Health (R01 DK61470) and Rally Foundation for Cancer Research. Funding Information: This work was supported by grants from the National Institutes of Health (R01 DK61470) and Rally Foundation for Cancer Research. The Authors thank Karen Martin for her aid in manuscript preparation. Flow Cytometry experiments were performed in the VMC Flow Cytometry Shared Resource. The VMC Flow Cytometry Shared Resource is supported by the Vanderbilt Ingram Cancer Center (P30CA68485) and the Vanderbilt Digestive Disease Research Center (DK058404). Publisher Copyright: © 2018 International Institute of Anticancer Research. All Rights Reserved.

PY - 2018/2

Y1 - 2018/2

N2 - 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.

AB - 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.

KW - Differentiation

KW - Neuroblastoma

KW - Proliferation

KW - SIRT6

KW - Sirtuins

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DO - 10.21873/anticanres.12268

M3 - Article

C2 - 29374686

AN - SCOPUS:85041652076

SN - 0250-7005

VL - 38

SP - 647

EP - 654

JO - Anticancer Research

JF - Anticancer Research

IS - 2

ER -

Inhibition of sirtuin 6 induces neuroblastoma differentiation

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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Cite this