LDH-Apromotes epithelial-mesenchymal transition by upregulating ZEB2 in intestinal-type gastric cancer.

Abstract

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.

• Authors: Yongjie Zhang, Sen Lin, Yan Chen, Fei Yang, Shenlin Liu
• Journal: OncoTargets and therapy (Onco Targets Ther) Vol. 11 Pg. 2363-2373 ( 2018) ISSN: 1178-6930 [Print] New Zealand
• PMID: 29740212 (Publication Type: Journal Article)