CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
School of Life Sciences and Technology, Shanghai Tech University, Shanghai, China.
Carcinogenesis. 2020 Apr 22;41(2):214-222. doi: 10.1093/carcin/bgz098.
Adenosylmethionine decarboxylase 1 (AMD1) is a key enzyme involved in biosynthesis of polyamines including spermidine and spermine. The potential function of AMD1 in human gastric cancers is unknown. We analyzed AMD1 expression level in 319 human gastric cancer samples together with the adjacent normal tissues. The protein expression level of AMD1 was significantly increased in human gastric cancer samples compared with their corresponding para-cancerous histological normal tissues (P < 0.0001). The expression level of AMD1 was positively associated with Helicobactor pylori 16sRNA (P < 0.0001), tumor size (P < 0.0001), tumor differentiation (P < 0.05), tumor venous invasion (P < 0.0001), tumor lymphatic invasion (P < 0.0001), blood vessel invasion (P < 0.0001), and tumor lymph node metastasis (TNM) stage (P < 0.0001). Patients with high expression of AMD1 had a much shorter overall survival than those with normal/low expression of AMD1. Knockdown of AMD1 in human gastric cancer cells suppressed cell proliferation, colony formation and cell migration. In a tumor xenograft model, knockdown of AMD1 suppressed the tumor growth in vivo. Inhibition of AMD1 by an inhibitor SAM486A in human gastric cancer cells arrested cell cycle progression during G1-to-S transition. Collectively, our studies at the cellular, animal and human levels indicate that AMD1 has a tumorigenic effect on human gastric cancers and affect the prognosis of the patients.
腺苷甲硫氨酸脱羧酶 1（AMD1）是参与多胺包括精脒和精胺生物合成的关键酶。AMD1 在人类胃癌中的潜在功能尚不清楚。我们分析了 319 例人类胃癌样本及其相邻正常组织中的 AMD1 表达水平。与相应的癌旁组织正常组织相比，人类胃癌样本中 AMD1 的蛋白表达水平显著升高（P < 0.0001）。AMD1 的表达水平与幽门螺杆菌 16sRNA（P < 0.0001）、肿瘤大小（P < 0.0001）、肿瘤分化（P < 0.05）、肿瘤静脉浸润（P < 0.0001）、肿瘤淋巴浸润（P < 0.0001）、血管浸润（P < 0.0001）和肿瘤淋巴结转移（TNM）分期（P < 0.0001）呈正相关。AMD1 高表达的患者总生存期明显短于 AMD1 正常/低表达的患者。在人胃癌细胞中敲低 AMD1 抑制细胞增殖、集落形成和细胞迁移。在肿瘤异种移植模型中，敲低 AMD1 抑制了体内肿瘤的生长。AMD1 抑制剂 SAM486A 抑制人胃癌细胞中 AMD1 的表达可阻滞细胞周期从 G1 期向 S 期的进展。综上所述，我们在细胞、动物和人体水平上的研究表明，AMD1 对人类胃癌具有致癌作用，并影响患者的预后。
