Galanin is an epigenetically silenced tumor suppressor gene in gastric cancer cells.

Daseul Yoon,Kieun Bae,Kyong-Ah Yoon,Jin Hee Kim,Min-Kyeong Lee,Hiromu Suzuki

doi:10.1371/journal.pone.0193275

Daseul Yoon, Kieun Bae + Show 4 more

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https://doi.org/10.1371/journal.pone.0193275

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Abstract

Galanin is a 30 amino-acid active neuropeptide that acts via three G-protein coupled galanin receptors, GALR1, GALR2 and GALR3. Recently, GALR1 was also suggested as a tumor suppressor gene that was frequently silenced in head and neck squamous cell carcinoma; moreover, galanin and GALR1 were reported to inhibit human oral cancer cell proliferation. However, the exact role of galanin in gastric cancer is unclear. Here, we describe the epigenetic silencing of galanin in human gastric cancer. Five gastric cancer cell lines (SNU-1, SNU-601, SNU-638, KATOIII, and AGS) showed a significant reduction in galanin expression that was restored by the demethylating agent 5-aza-2’-deoxycytidine. We confirmed the hypermethylation of CpG islands in the galanin promoter region by methylation-specific and bisulfate sequencing polymerase chain reaction (PCR). Interestingly, hypermethylated galanin did not affect galanin receptor expression. Exogenous galanin expression in silenced cells induced apoptosis and decreased phosphorylated Akt expression. Taken together, these data suggest that galanin hypermethylation impairs its tumor suppressor function in gastric cancer carcinogenesis.

Highlights

Galanin is a neuropeptide with a number of physiological actions that is distributed throughout the central and peripheral nervous systems
Human galanin is 6.6-kb long, with six exons that are translated into a 123 amino-acid prepropeptide; the galanin prepropeptide is processed to active galanin and galanin message associated peptide [1]
Galanin has a variety of nervous system effects, including nociception, hormone regulation, and glucose metabolism [5, 6], and galanin and its receptors are involved in cell proliferation and tumor progression

Summary

Introduction

Galanin is a neuropeptide with a number of physiological actions that is distributed throughout the central and peripheral nervous systems. Human galanin is 6.6-kb long, with six exons that are translated into a 123 amino-acid prepropeptide; the galanin prepropeptide is processed to active galanin and galanin message associated peptide [1]. Human galanin was isolated from the pituitary as a 30 amino-acid peptide with an additional non-amidated C-terminal residue [4]. Galanin has a variety of nervous system effects, including nociception, hormone regulation, and glucose metabolism [5, 6], and galanin and its receptors are involved in cell proliferation and tumor progression. Galanin and GALR1 inhibited human oral cancer cell proliferation by down-regulating cyclin D1 and activating cyclindependent kinase inhibitors [7].

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