摘要： 目的 探索长寿蛋白6（SIRT6）对胃癌预后的影响及作用机制。方法 利用GEO数据库中的GSE62254胃癌数据集分析SIRT6表达与预后及各临床病理学参数的相关性；基因集富集分析（GSEA）预测其可能参与胃癌调控的通路；敲减SIRT6后检测胃癌细胞迁移能力和相关蛋白表达的改变。结果 SIRT6低表达患者生存期明显缩短；GSEA结果提示SIRT6低表达与Wnt通路及细胞骨架蛋白调控密切相关；在胃癌细胞中敲减SIRT6后，胃癌细胞迁移能力增加，且β-catenin失活型磷酸化水平降低、intergrin α5表达上调。结论 SIRT6是胃癌预后的保护因素，下调其表达可通过活化Wnt通路及上调intergrin α5蛋白表达促进胃癌细胞迁移。

长寿蛋白6对胃癌预后的影响及作用机制

包博文, 梁金娥, 沈泽明, 金悦, 于诗彤, 刘云鹏, 车晓芳

中国医科大学附属第一医院肿瘤内科, 辽宁省肿瘤药物与生物治疗重点实验室, 沈阳 110001

收稿日期:2019-03-13出版日期:2020-09-30发布日期:2020-09-15
通讯作者:车晓芳E-mail:chexf_2015@126.com
作者简介:包博文(1993-),男,硕士研究生.
基金资助:辽宁省重点研发指导计划（2018225060）；辽宁省中央引导地方科技发展专项资金（2016007010）


关键词: 长寿蛋白6, 胃癌, 预后, 作用机制
Abstract: Objective To explore the prognostic value and mechanism of sirtuin 6 (SIRT6) in gastric cancer. Methods The correlation of SIRT6 expression with prognosis and clinicopathological parameters was analyzed using the GSE62254 gastric cancer dataset downloaded from the gene expression omnibus (GEO) database. Gene set enrichment analysis (GSEA) was performed to predict SIRT6-related pathways in gastric cancer. Following SIRT6 knockdown,the changes in migration ability and protein expression were also detected. Results The overall survival of patients with low expression of SIRT6 was significantly shorter than those with high SIRT6 expression (P<0.001). The GSEA results indicated that low SIRT6 expression was closely related to the Wnt signaling pathway and regulation of actin cytoskeleton. SIRT6 knockdown in gastric cancer cells increased the cell migration ability,decreased the phosphorylation level of inactivated β-catenin,and upregulated the expression of intergrin α5. Conclusion SIRT6 plays a protective role in gastric cancer prognosis,and the downregulation of SIRT6 could promote gastric cancer cell migration by activating the Wnt signaling pathway and upregulating intergrin α5.
Key words: sirtuin 6, gastric cancer, prognosis, mechanism
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