The histone acetyltransferase GCN5 expression is elevated and regulated by c-Myc and E2F1 transcription factors in human colon cancer

Yan Wei Yin, Hong Jian Jin, Wenjing Zhao, Beixue Gao, Jiangao Fang, Junmin Wei, Donna Zhang, Jianing Zhang, Deyu Fang

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

The histone acetyltransferase GCN5 has been suggested to be involved in promoting cancer cell growth. But its role in human colon cancer development remains unknown. Herein we discovered that GCN5 expression is significantly upregulated in human colon adenocarcinoma tissues. We further demonstrate that GCN5 is upregulated in human colon cancer at the mRNA level. Surprisingly, two transcription factors, the oncogenic c-Myc and the proapoptotic E2F1, are responsible for GCN5 mRNA transcription. Knockdown of c-Myc inhibited colon cancer cell proliferation largely through downregulating GCN5 transcription, which can be fully rescued by the ectopic GCN5 expression. In contrast, E2F1 expression induced human colon cancer cell death, and suppression of GCN5 expression in cells with E2F1 overexpression further facilitated cell apoptosis, suggesting that GCN5 expression is induced by E2F1 as a possible negative feedback in suppressing E2F1-mediated cell apoptosis. In addition, suppression of GCN5 with its specific inhibitor CPTH2 inhibited human colon cancer cell growth. Our studies reveal that GCN5 plays a positive role in human colon cancer development, and its suppression holds a great therapeutic potential in antitumor therapy.

Original languageEnglish (US)
Pages (from-to)187-196
Number of pages10
JournalGene Expression
Volume16
Issue number4
DOIs
StatePublished - 2015

Fingerprint

E2F1 Transcription Factor
Colonic Neoplasms
Apoptosis
Messenger RNA
Growth
human KAT2A protein
Colon
Adenocarcinoma
Cell Death
Transcription Factors
Down-Regulation
Cell Proliferation
Therapeutics

Keywords

  • C-Myc
  • Colon cancer
  • E2F1
  • Gene transcription
  • General control nonrepressed protein 5 (GCN5)

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Medicine(all)

Cite this

The histone acetyltransferase GCN5 expression is elevated and regulated by c-Myc and E2F1 transcription factors in human colon cancer. / Yin, Yan Wei; Jin, Hong Jian; Zhao, Wenjing; Gao, Beixue; Fang, Jiangao; Wei, Junmin; Zhang, Donna; Zhang, Jianing; Fang, Deyu.

In: Gene Expression, Vol. 16, No. 4, 2015, p. 187-196.

Research output: Contribution to journalArticle

Yin, Yan Wei ; Jin, Hong Jian ; Zhao, Wenjing ; Gao, Beixue ; Fang, Jiangao ; Wei, Junmin ; Zhang, Donna ; Zhang, Jianing ; Fang, Deyu. / The histone acetyltransferase GCN5 expression is elevated and regulated by c-Myc and E2F1 transcription factors in human colon cancer. In: Gene Expression. 2015 ; Vol. 16, No. 4. pp. 187-196.
@article{4dad8e48581d4622a3c13c4ea4daf145,
title = "The histone acetyltransferase GCN5 expression is elevated and regulated by c-Myc and E2F1 transcription factors in human colon cancer",
abstract = "The histone acetyltransferase GCN5 has been suggested to be involved in promoting cancer cell growth. But its role in human colon cancer development remains unknown. Herein we discovered that GCN5 expression is significantly upregulated in human colon adenocarcinoma tissues. We further demonstrate that GCN5 is upregulated in human colon cancer at the mRNA level. Surprisingly, two transcription factors, the oncogenic c-Myc and the proapoptotic E2F1, are responsible for GCN5 mRNA transcription. Knockdown of c-Myc inhibited colon cancer cell proliferation largely through downregulating GCN5 transcription, which can be fully rescued by the ectopic GCN5 expression. In contrast, E2F1 expression induced human colon cancer cell death, and suppression of GCN5 expression in cells with E2F1 overexpression further facilitated cell apoptosis, suggesting that GCN5 expression is induced by E2F1 as a possible negative feedback in suppressing E2F1-mediated cell apoptosis. In addition, suppression of GCN5 with its specific inhibitor CPTH2 inhibited human colon cancer cell growth. Our studies reveal that GCN5 plays a positive role in human colon cancer development, and its suppression holds a great therapeutic potential in antitumor therapy.",
keywords = "C-Myc, Colon cancer, E2F1, Gene transcription, General control nonrepressed protein 5 (GCN5)",
author = "Yin, {Yan Wei} and Jin, {Hong Jian} and Wenjing Zhao and Beixue Gao and Jiangao Fang and Junmin Wei and Donna Zhang and Jianing Zhang and Deyu Fang",
year = "2015",
doi = "10.3727/105221615X14399878166230",
language = "English (US)",
volume = "16",
pages = "187--196",
journal = "Gene Expression",
issn = "1052-2166",
publisher = "Cognizant Communication Corporation",
number = "4",

}

TY - JOUR

T1 - The histone acetyltransferase GCN5 expression is elevated and regulated by c-Myc and E2F1 transcription factors in human colon cancer

AU - Yin, Yan Wei

AU - Jin, Hong Jian

AU - Zhao, Wenjing

AU - Gao, Beixue

AU - Fang, Jiangao

AU - Wei, Junmin

AU - Zhang, Donna

AU - Zhang, Jianing

AU - Fang, Deyu

PY - 2015

Y1 - 2015

N2 - The histone acetyltransferase GCN5 has been suggested to be involved in promoting cancer cell growth. But its role in human colon cancer development remains unknown. Herein we discovered that GCN5 expression is significantly upregulated in human colon adenocarcinoma tissues. We further demonstrate that GCN5 is upregulated in human colon cancer at the mRNA level. Surprisingly, two transcription factors, the oncogenic c-Myc and the proapoptotic E2F1, are responsible for GCN5 mRNA transcription. Knockdown of c-Myc inhibited colon cancer cell proliferation largely through downregulating GCN5 transcription, which can be fully rescued by the ectopic GCN5 expression. In contrast, E2F1 expression induced human colon cancer cell death, and suppression of GCN5 expression in cells with E2F1 overexpression further facilitated cell apoptosis, suggesting that GCN5 expression is induced by E2F1 as a possible negative feedback in suppressing E2F1-mediated cell apoptosis. In addition, suppression of GCN5 with its specific inhibitor CPTH2 inhibited human colon cancer cell growth. Our studies reveal that GCN5 plays a positive role in human colon cancer development, and its suppression holds a great therapeutic potential in antitumor therapy.

AB - The histone acetyltransferase GCN5 has been suggested to be involved in promoting cancer cell growth. But its role in human colon cancer development remains unknown. Herein we discovered that GCN5 expression is significantly upregulated in human colon adenocarcinoma tissues. We further demonstrate that GCN5 is upregulated in human colon cancer at the mRNA level. Surprisingly, two transcription factors, the oncogenic c-Myc and the proapoptotic E2F1, are responsible for GCN5 mRNA transcription. Knockdown of c-Myc inhibited colon cancer cell proliferation largely through downregulating GCN5 transcription, which can be fully rescued by the ectopic GCN5 expression. In contrast, E2F1 expression induced human colon cancer cell death, and suppression of GCN5 expression in cells with E2F1 overexpression further facilitated cell apoptosis, suggesting that GCN5 expression is induced by E2F1 as a possible negative feedback in suppressing E2F1-mediated cell apoptosis. In addition, suppression of GCN5 with its specific inhibitor CPTH2 inhibited human colon cancer cell growth. Our studies reveal that GCN5 plays a positive role in human colon cancer development, and its suppression holds a great therapeutic potential in antitumor therapy.

KW - C-Myc

KW - Colon cancer

KW - E2F1

KW - Gene transcription

KW - General control nonrepressed protein 5 (GCN5)

UR - http://www.scopus.com/inward/record.url?scp=84957418373&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84957418373&partnerID=8YFLogxK

U2 - 10.3727/105221615X14399878166230

DO - 10.3727/105221615X14399878166230

M3 - Article

C2 - 26637399

AN - SCOPUS:84957418373

VL - 16

SP - 187

EP - 196

JO - Gene Expression

JF - Gene Expression

SN - 1052-2166

IS - 4

ER -