Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian 363000, P.R. China.
United Hospital of Fujian Medical University, Fuzhou, Fujian 350001, P.R. China.
Oncol Rep. 2014 Jun;31(6):2593-600. doi: 10.3892/or.2014.3135. Epub 2014 Apr 14.
The present study aimed to investigate the involvement of the Suv39H1 histone methyltransferase in the epigenetic changes in the euchromatic promoter in gastric carcinoma. We retrospectively analyzed the protein of Suv39H1 and tri-methylated histone H3 lysine 9 (H3K9) and histone H3 lysine 4 (H3K4) in 175 cases of gastric carcinoma by immunohistochemistry. Suv39H1 was depleted by siRNA, and cell apoptosis and cell proliferation were assessed by TUNEL and MTT assays, respectively. Histone methylated H3K9 and histone acetylated H3 and H4 were evaluated by western blotting. We found that the expression of Suv39H1 and tri-methylated H3K9 in gastric carcinoma was higher than that in benign gastric diseases (p<0.05). Tri-methylated H3K4 was similar in both tissue types (p>0.05). Both Suv39H1 and tri-methylated H3K9 were positively correlated with the degree of differentiation, depth of infiltration and lymphatic invasion (p<0.05) in gastric carcinoma. In addition, tri-methylated H3K9 was positively correlated with tumor stage, and node and metastatic statuses (p<0.05). Activation of Suv39H1 and overexpression of H3K9 tri-methylation may play an important role in tumorigenesis. They may be useful as a predictor for poor prognosis in gastric carcinoma. Silencing of the Suv39H1 gene decreased tri-methylated H3K9 and increased histone H3 acetylation, which caused activation of gene transcription, while there was no change in histone H4 acetylation. Depletion of Suv39H1 induced apoptosis and inhibited cell proliferation in the gastric cancer MGC803 cell line, while decreasing BCL-2, pro-caspase-9, pro-caspase-3 and C-myc. Suv39H1 may be a potential gene target for anti-gastric carcinoma therapy.
本研究旨在探讨 Suv39H1 组蛋白甲基转移酶在胃癌染色质酶促修饰中的作用。我们通过免疫组化法分析了 175 例胃癌标本中 Suv39H1 蛋白和三甲基化组蛋白 H3 赖氨酸 9（H3K9）及组蛋白 H3 赖氨酸 4（H3K4）的表达。采用 siRNA 方法沉默 Suv39H1，通过 TUNEL 及 MTT 检测细胞凋亡和增殖。Western blot 法检测组蛋白甲基化 H3K9 和组蛋白乙酰化 H3、H4。结果显示，胃癌组织中 Suv39H1 及三甲基化 H3K9 的表达高于良性胃病（p<0.05），两种组织中三甲基化 H3K4 的表达无差异（p>0.05）。Suv39H1 和三甲基化 H3K9 的表达与胃癌的分化程度、浸润深度和淋巴转移相关（p<0.05）。此外，三甲基化 H3K9 与肿瘤分期、淋巴结转移和远处转移相关（p<0.05）。Suv39H1 的激活和 H3K9 三甲基化的过度表达可能在肿瘤发生中发挥重要作用，有望作为胃癌不良预后的预测指标。沉默 Suv39H1 基因可降低三甲基化 H3K9 并增加组蛋白 H3 乙酰化，从而激活基因转录，而组蛋白 H4 乙酰化无变化。Suv39H1 沉默可诱导胃癌 MGC803 细胞凋亡和增殖抑制，同时下调 BCL-2、pro-caspase-9、pro-caspase-3 和 C-myc。Suv39H1 可能是胃癌治疗的潜在基因靶点。
