Institute for Regenerative Medicine, Yanbian University College of Medicine, Yanji 133002, Jilin Province, PR China; Department of Histology and Embryology, Yanbian University College of Medicine, Yanji 133002, Jilin Province, PR China.
Institute for Regenerative Medicine, Yanbian University College of Medicine, Yanji 133002, Jilin Province, PR China; Department of Pathology, Yanbian University College of Medicine, Yanji 133002, Jilin Province, PR China.
Exp Mol Pathol. 2020 Dec;117:104560. doi: 10.1016/j.yexmp.2020.104560. Epub 2020 Oct 28.
SETD8 is a lysine methyltransferase containing an SET domain, which is involved in the carcinogenesis of many cancer types through monomethylation of the histone H4 lysine 20. However, its prognostic value and underlying mechanisms in gastric adenocarcinoma (GA) have not been extensively studied. Here, we assessed SETD8 expression and its relationship with clinicopathological parameters, cancer stemness-related proteins, cell cycle-related proteins, and PI3K/Akt pathway proteins in GA. SETD8 expression in GA tissues was correlated with the primary tumor stage, lymph node metastasis, tumor size, gross type, and clinical stage. SETD8 was an independent predictor of poor overall survival of patients with GA. Cox regression analysis showed that SETD8 is a potential biomarker of unfavorable clinical outcomes in patients with GA. Moreover, SETD8 overexpression was associated with cancer stemness-related genes, cell cycle-related genes, and PI3K/Akt/NF-κB pathway genes in clinical GA tissue samples. SETD8 silencing downregulated the expression of cancer stemness-associated genes (LSD1 and SOX2) and inhibited GA cell proliferation, spheroid formation, invasion, and migration. Additionally, LY294002 significantly reduced the expression of SETD8, pAkt-Ser473, pPI3K-p85, and NFκB-p65 in MKN74 and MKN28 cells. SETD8 may be a novel cancer stemness-associated protein and potential prognostic biomarker in GA.
SETD8 是一种赖氨酸甲基转移酶，含有 SET 结构域，它通过组蛋白 H4 赖氨酸 20 的单甲基化参与许多癌症类型的致癌作用。然而，其在胃腺癌 (GA) 中的预后价值及其潜在机制尚未得到广泛研究。在这里，我们评估了 SETD8 在 GA 组织中的表达及其与临床病理参数、癌症干细胞相关蛋白、细胞周期相关蛋白和 PI3K/Akt 通路蛋白的关系。GA 组织中 SETD8 的表达与原发肿瘤分期、淋巴结转移、肿瘤大小、大体类型和临床分期相关。SETD8 是 GA 患者总生存期不良的独立预测因子。Cox 回归分析表明，SETD8 是 GA 患者不良临床结局的潜在生物标志物。此外，在临床 GA 组织样本中，SETD8 过表达与癌症干细胞相关基因、细胞周期相关基因和 PI3K/Akt/NF-κB 通路基因相关。SETD8 沉默下调了癌症干细胞相关基因（LSD1 和 SOX2）的表达，并抑制了 GA 细胞的增殖、球体形成、侵袭和迁移。此外，LY294002 显著降低了 MKN74 和 MKN28 细胞中 SETD8、pAkt-Ser473、pPI3K-p85 和 NFκB-p65 的表达。SETD8 可能是 GA 中一种新型的癌症干细胞相关蛋白和潜在的预后生物标志物。
