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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


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Geoffrey Pietersz

Video abstract presented by Shenlin Liu.

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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

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