AEG-1 promotes the growth of gastric cancer through the upregulation of eIF4E expression

• Main Authors: Wu S, Zhang Z, Wu D, Chen H, Qian X, Wang X, Huang W
• Format: Article
• Language: English
• Published: Dove Medical Press 2019-07-01
• Series: OncoTargets and Therapy
• Subjects: AEG-1; eIF4E; cyclin D1; gastric cancer
• Online Access: https://www.dovepress.com/aeg-1-promotes-the-growth-of-gastric-cancer-through-the-upregulation-o-peer-reviewed-article-OTT

Shengjie Wu,1,2,* Zuhao Zhang,1,* Dandan Wu,1,3 Hongling Chen,1 Xixi Qian,1 Xuerong Wang,1 Wenbin Huang41Department of Pharmacology, Nanjing Medical University, Nanjing, Jiangsu Province 210029, People’s Republic of China; 2Department of Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province 310016, People’s Republic of China; 3Department of Basic Medicine, Kangda College of Nanjing Medical University, Lianyungang, Jiangsu Province 222000, People’s Republic of China; 4Department of Pathology, Nanjing Medical University Affiliated Nanjing Hospital (Nanjing First Hospital), Nanjing, Jiangsu Province 210006, People’s Republic of China*These authors contributed equally to this workBackground: AEG-1 has been proven to be tumor enhancer in gastric cancer. However, its mechanism has not yet been fully clarified.Methods: Gain-of-function and loss-of-function experiments were conducted to determine the role of eIF4E in AEG-1-induced growth of gastric cancer cells and xenografts of a nude mouse model. Western blot analysis and SRB assay were used to determine the protein expression levels and survival cell numbers.Results: Silencing the expression of AEG-1 inhibited the growth of gastric cancer cells in parallel with a decreased eIF4E and cyclin D1 expression; however, the overexpression of AEG-1 promoted cell growth and increased eIF4E and cyclin D1 expression. Moreover, the overexpression of eIF4E partially reversed the AEG-1 silencing-induced reduction of cyclin D1 and the inhibition of cell growth. An eIF4E knockdown also partially reversed the AEG-1 overexpression-induced upregulation of cyclin D1 and cell growth. Notably, manipulating the expression of eIF4E did not affect the expression of AEG-1. Finally, the silencing of AEG-1 expression inhibited the growth of SGC-7901 xenografts in parallel with the downregulation of eIF4E and cyclin D1 expression in the nude mouse model.Conclusion: AEG-1 promoted the growth of gastric cancer through upregulation of eIF4E/cyclin D1 signaling pathway.Keywords: AEG-1, eIF4E, cyclin D1, gastric cancer