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Abstract：
Invasion and metastasis are the leading causes of death in individuals with malignant tumors, including gastric cancer. In this study, we aim to explore the effect and related mechanisms of methionine restriction (MR) on gastric carcinoma metastasis. In the MR cell model, gastric carcinoma cells are cultured in the MR medium, and in the animal model, BALB/c nude rodents are administered with a methionine-free diet after receiving injections of MKN45 cells into the caudal vein. Transwell assay is used to detect cell invasion and migration. Chromatin immunoprecipitation is performed to investigate the levels of H3K9me2, H3K27Ac, and H3K27me3 in the E-cadherin promoter. The results show that MR inhibits gastric carcinoma cell migration, invasion, and lung metastasis. MR increases E-cadherin while reducing the H3K27me3 level in the E-cadherin promoter. E-cadherin expression in gastric carcinoma cells is adversely regulated by HDAC2. Overexpressing HDAC2 reduces the H3K27Ac level in the E-cadherin promoter, while interfering with HDAC2 increases the H3K27Ac level. HDAC2 interference under MR conditions further upregulates E-cadherin expression and inhibits gastric carcinoma cell migration, invasion, and lung metastasis. MR combined with HDAC2 interference promotes E-cadherin expression by mediating the methylation and acetylation of E-cadherin, thus inhibiting the invasion, migration, and lung metastasis of gastric carcinoma cells. Our study provides a new theoretical basis for the inhibitory effect of MR on gastric cancer.
摘要：
侵袭和转移是恶性肿瘤患者死亡的主要原因，包括胃癌.在这项研究中,目的探讨甲硫氨酸限制（MR）对胃癌转移的影响及相关机制。在MR细胞模型中,胃癌细胞在MR培养基中培养，在动物模型中，BALB/c裸啮齿动物在接受将MKN45细胞注射到尾静脉后，给予无蛋氨酸饮食。Transwell测定法用于检测细胞侵袭和迁移。进行染色质免疫沉淀以研究H3K9me2，H3K27Ac的水平，和E-钙粘蛋白启动子中的H3K27me3。结果显示MR抑制胃癌细胞迁移,入侵,和肺转移。MR增加E-钙粘蛋白,同时降低E-钙粘蛋白启动子中的H3K27me3水平。E-cadherin在胃癌细胞中的表达受到HDAC2的不利调节。过表达HDAC2降低了E-cadherin启动子中的H3K27Ac水平,而干扰HDAC2会增加H3K27Ac水平。在MR条件下HDAC2干扰进一步上调E-cadherin表达并抑制胃癌细胞迁移,入侵,和肺转移。MR联合HDAC2干扰通过介导E-cadherin甲基化和乙酰化促进E-cadherin表达,从而抑制入侵，迁移,胃癌细胞的肺转移。本研究为MR对胃癌的抑制作用提供了新的理论依据。
