Epigenetic Silencing of the Putative Tumor Suppressor Gene GLDC (Glycine Dehydrogenase) in Gastric Carcinoma

Abstract

Background: The metabolic enzyme, glycine dehydrogenase (GLDC), involved in glycine metabolism, is known to be involved in non-ketotic hyperglycinemia but not in cancer. Herein, we investigated GLDC expression and its promoter methylation in gastric cancer (GC).

Materials and methods: GLDC expression and epigenetics were investigated using GC cell lines and tissues. Functional studies were also performed for identification of a correlation between methylated GLDC genes and gastric cancer progression.

Results: The results of the study can be summarized as follows: (i) GLDC was silenced in GC cell lines and tissues. The down-regulation of GLDC was closely linked to promoter methylation. (ii) Knockdown of GLDC increased cell proliferation, migration, invasion, colony formation and reduced apoptosis. (iii) In GC tissues, hypermethylation of GLDC had a significant correlation with down-regulation of the GLDC protein compared to normal gastric tissues.

Conclusion: GLDC is a putative tumor suppressor gene involved in gastric cancer progression and hypermethylation of the GLDC promoter regulates its transcriptional silencing.

Keywords: DNA methylation; Glycine dehydrogenase; stomach neoplasms; tumor suppressor gene.