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

By: Hyae Lim Min, Jin Kim, Woo Ho Kim, Bo Gun Jang, Min A Kim

Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea Department of Cancer Biology, Seoul National University College of Medicine, Seoul, Republic of Korea.
2016-1-2; doi:

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

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.