Abstract

Gastric cancer is the fourth most common cancer worldwide, with a low 5-year survival rate. Epigenetic modification plays pivotal roles in gastric cancer development. However, the role of histone-modifying enzymes in gastric cancer remains largely unknown. Here we report that Sirt7, a NAD+-dependent class III histone deacetylase, is over-expressed in human gastric cancer tissues. Sirt7 level is significantly correlated with disease stage, metastasis and survival. Knockdown of Sirt7 in gastric cancer cells inhibits cell proliferation and colony formation in vitro. In vivo subcutaneous xenograft results also show that Sirt7 knockdown can markedly repress gastric cancer cell growth. In addition, Sirt7 depletion induces apoptosis in gastric cancer cells via up-regulating expression of pro-apoptotic proteins and down-regulating anti-apoptotic proteins. Mechanically, Sirt7 binds to the promoter of miR-34a and deacetylases the H3K18ac, thus represses miR-34a expression. Reversely, depletion of miR-34a inhibits gastric cancer apoptosis induced by Sirt7 knockdown and restores cellular capacity of proliferation and colony formation. miR-34a depletion reduces Sirt7-knockdown-induced arrest of gastric growth. Finally, miR-34a is tightly associated with survival of patients with gastric cancer.

Details

Title
RETRACTED ARTICLE: Sirt7 promotes gastric cancer growth and inhibits apoptosis by epigenetically inhibiting miR-34a
Author
Zhang, Shun 1 ; Chen, Ping 2 ; Huang, Zuoan 1 ; Hu, Xiaorong 1 ; Chen, Mengting 3 ; Hu, Shanshan 3 ; Hu, Yixin 3 ; Cai, Ting 1 

 Stem Cell Laboratory, Ningbo No.2 Hospital, Ningbo, Zhejiang, China (GRID:grid.459833.0) (ISNI:0000 0004 1799 3336) 
 Gastrointestinal and Hernia Ward, Ningbo No.2 Hospital, Ningbo, Zhejiang, China (GRID:grid.459833.0) (ISNI:0000 0004 1799 3336) 
 School of Medicine, Ningbo University, Department of Internal Medicine, Ningbo, Zhejiang, China (GRID:grid.203507.3) (ISNI:0000 0000 8950 5267) 
Pages
9787
Publication year
2015
Publication date
2015
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2829617332
Copyright
© The Author(s) 2015. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.