Back to Journals » OncoTargets and Therapy » Volume 11

LDH-A promotes epithelial–mesenchymal transition by upregulating ZEB2 in intestinal-type gastric cancer

Authors Zhang Y, Lin S, Chen Y, Yang F, Liu S

Received 24 January 2018

Accepted for publication 11 March 2018

Published 27 April 2018 Volume 2018:11 Pages 2363—2373

DOI https://doi.org/10.2147/OTT.S163570

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Andrew Yee

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Geoffrey Pietersz


Video abstract presented by Shenlin Liu.

Views: 35

Yongjie Zhang,1,2,* Sen Lin,3,* Yan Chen,2,* Fei Yang,2 Shenlin Liu1

1Department of Gastroenterology, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 2Department of Medical Oncology, Huai’an Hospital to Xuzhou Medical University, Huai’an, Jiangsu, People’s Republic of China; 3Clinical Laboratory, Huai’an Hospital to Xuzhou Medical University, Huai’an, Jiangsu, People’s Republic of China

*These authors contributed equally to this work

Introduction: Epithelial-mesenchymal transition (EMT) is regarded as a crucial process of invasion and metastasis, which contribute greatly to cancer-related relapse and death. Based on research results that hypoxia can trigger gastric cancer EMT and decreasing lactate production can selectively kill hypoxic cancer cells, we infer that lactate dehydrogenase A (LDH-A) transforming pyruvate into lactate is at least in part responsible for poor prognosis of gastric cancer.
Materials and methods:
We used siRNA to knock down LDH-A in intestinal-type gastric cancer (ITGC) cell lines SGC7901 and BGC823. Western blot and RT-PCR were applied to detect mRNA and protein expression of EMT-related genes, respectively. Transwell invasion assay and migration assay were applied to study invasive and migratory abilities, respectively. Survival analysis was used to evaluate prognostic values.
Results and conclusion:
The results of in vitro experiment demonstrated that LDH-A facilitates ITGC cells’ invasion and migration by upregulating ZEB2. The positive correlation between LDH-A and ZEB2 was verified in 371 ITGC specimens. Survival analysis indicated that co-expression of LDH-A/ZEB2 had synergetic power to predict overall survival. Thus, we conclude that the close relationship between LDH-A and ZEB2 may offer a potential therapeutic strategy for ITGC.

Keywords: intestinal-type gastric cancer, LDH-A, ZEB2, epithelial–mesenchymal transition, Warburg effect, glycolysis

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]