Department of Biochemistry, College of Veterinary Medicine, Konkuk University, Seoul, Korea.
Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea.
PLoS One. 2018 Feb 20;13(2):e0193275. doi: 10.1371/journal.pone.0193275. eCollection 2018.
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.
甘丙肽是一种 30 个氨基酸的活性神经肽，通过三种 G 蛋白偶联甘丙肽受体（GALR1、GALR2 和 GALR3）发挥作用。最近，GALR1 也被认为是一种肿瘤抑制基因，在头颈部鳞状细胞癌中经常失活；此外，甘丙肽和 GALR1 被报道可抑制人口腔癌细胞的增殖。然而，甘丙肽在胃癌中的确切作用尚不清楚。在这里，我们描述了甘丙肽在人胃癌中的表观遗传沉默。五种胃癌细胞系（SNU-1、SNU-601、SNU-638、KATOIII 和 AGS）显示甘丙肽表达显著减少，而 5-氮杂-2'-脱氧胞苷去甲基化剂可使其恢复。我们通过甲基化特异性和亚硫酸氢盐测序聚合酶链反应（PCR）证实了甘丙肽启动子区域 CpG 岛的高甲基化。有趣的是，高甲基化的甘丙肽并不影响甘丙肽受体的表达。沉默细胞中外源甘丙肽的表达诱导细胞凋亡并降低磷酸化 Akt 的表达。总之，这些数据表明甘丙肽的高甲基化损害了其在胃癌发生中的肿瘤抑制功能。
