Back to Journals » Cancer Management and Research » Volume 12

Knockdown of ATAD2 Inhibits Proliferation and Tumorigenicity Through the Rb-E2F1 Pathway and Serves as a Novel Prognostic Indicator in Gastric Cancer

Authors Zhou X, Ji H, Ye D, Li H, Liu F, Li H, Xu J, Li Y, Xiang F

Received 25 August 2019

Accepted for publication 24 December 2019

Published 15 January 2020 Volume 2020:12 Pages 337—351

DOI https://doi.org/10.2147/CMAR.S228629

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Antonella D'Anneo


Xuan Zhou, 1,* Huihui Ji, 2,* Dongxue Ye, 2 Hong Li, 1 Fen Liu, 2 Haiyan Li, 2 Jin Xu, 1 Yujun Li, 1 Fenggang Xiang 1, 2

1Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao 266000, People’s Republic of China; 2Department of Pathology, School of Basic Medicine, Qingdao University, Qingdao 266071, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Fenggang Xiang
Department of Pathology, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao 266000, People’s Republic of China
Email xiangfenggang0532@163.com

Introduction: The aim of the present study was to examine the expression of ATAD2 in gastric cancer (GC) specimens and to evaluate its correlation with clinicopathologic features, including survival of GC patients. The potential roles of ATAD2 in the GC cell proliferation, apoptosis, and tumour growth were further explored.
Materials and Methods: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blotting and immunohistochemistry (IHC) were applied to determine the mRNA and protein expression of ATAD2 in GC and corresponding adjacent non-tumourous specimens. The relationship between ATAD2 expression and clinicopathological features of GC patients was analysed. Kaplan-Meier analysis was performed to assess the prognostic value of ATAD2 expression levels. The proliferation, colony formation, apoptosis and tumorigenesis roles of ATAD2 were measured using in vitro and in vivo experiments.
Results: The expression of ATAD2 mRNA and protein was overexpressed in GC tissues compared with corresponding adjacent non-tumourous tissues. ATAD2 expression was significantly correlated with tumour size, tumour differentiation, and clinical tumour-node-metastasis (TNM) stage. Patients with high ATAD2 expression were likely to experience significantly shorter postoperative overall survival (OS) and disease-free survival (DFS). Multivariate Cox analysis suggested ATAD2 as an independent variable for OS and DFS. Knockdown of ATAD2 significantly suppressed cell proliferation, colony formation in vitro and tumorigenicity in vivo. Cell cycle and apoptotic assays showed that the anti-proliferative effect of pLV-ATAD2 shRNA was mediated by arresting cells in the G1 phase and inducing cell apoptosis. Silencing of ATAD2 reduced the expression of cyclinD1, ppRb, E2F1 and cyclinE and upregulated the expression of cleaved-PARP and cleaved-Caspase 3.
Conclusion: Our study indicated that ATAD2 plays an important role in the process of tumorigenesis and progression in GC, and it could serve as a novel prognostic biomarker and a therapeutic target for the treatment of GC patients.

Keywords: ATAD2, gastric cancer, proliferation, apoptosis, prognosis

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]