沉默信息调节因子1在消化系统肿瘤中的作用

The Role of SIRT1 in Tumors of the Digestive System

沉默信息调节因子1(SIRT1)是Sirtuin家族中的一员,属于烟酰胺(NAD+)依赖的Ⅲ类组蛋白去乙酰化酶,能通过对多种非组蛋白及组蛋白赖氨酸残基进行去乙酰化修饰调节基因表达。近来的研究发现,SIRT1不仅能使肿瘤抑制因子去乙酰化,促进肿瘤发生,还能使肿瘤促进因子去乙酰化,抑制肿瘤发生。SIRT1与肿瘤的生物学特性密切相关,影响肿瘤分期及患者预后。在消化系统肿瘤中,SIRT1具有双面性,既可作为抑癌因子,也可发挥癌因子的作用。近年来,许多研究对SIRT1在肿瘤中的作用靶点及相关信号通路做了深入研究,关于SIRT1在肿瘤中作用机制的新研究不断出现。SIRT1已成为人们攻克肿瘤的一个研究热点。本文通过对SIRT1在肿瘤中的双重作用,尤其是在消化系统肿瘤中的不同作用靶点和参与的信号通路作一综述,希望为临床上治疗消化系统肿瘤提供更有说服力的证据。

SIRT1,a member of the Sirtuin family,is a class Ⅲ NAD＋-dependent histone deacetylase that regulates gene expression by deacetylating lysine residues of various non-histone and histone proteins. Recent studies have found that SIRT1 not only deacetylates tumor suppressors,promotes tumorigenesis,but also deacetylates tumor-promoting factors and inhibits tumorigenesis. Furthermore,SIRT1 closely regulates the biological characteristics of tumors,affecting the tumor staging and prognosis of patients. In the tumors of the digestive system,SIRT1 has dual roles： a tumor suppressor,as well as a tumor promoter. In recent years,researchers have studied intensively the targets of SIRT1 in tumors and the related signal pathways,and have uncovered new mechanism of SIRT1 in tumors. SIRT1 has therefore become a hot research topic for tumor therapy. Here we review the dual roles of SIRT1 in tumorigenesis,in particular its distinct targets and the related signaling pathways in tumors of the digestive system,aiming provide more convincing evidence for clinical treatment.