SIRT7在肿瘤发生发展中的研究进展

The Emerging Roles of SIRT7 in Tumorigenesis

Sirtuins蛋白家族是一类高度保守的烟酰胺腺嘌呤二核苷酸(NAD+)依赖的组蛋白去乙酰化酶。哺乳动物中的Sirtuins包括七种亚型:SIRT1-SIRT7,作为Sirtuins蛋白家族成员之一,SIRT7定位于核仁,是一种高度特异性的H3K18Ac(组蛋白H3的乙酰化赖氨酸残基18)去乙酰化酶。SIRT7的作用底物包括组蛋白和非组蛋白,底物的多样性决定着它参与体内多种细胞活动,如:细胞增殖、细胞新陈代谢、DNA损伤和应激反应等,并与肿瘤的发生发展密切相关。SIRT7在乳腺癌、甲状腺癌、卵巢癌、宫颈癌、胃癌、结直肠癌和肝细胞癌等多种肿瘤中高表达;而在头颈部鳞癌和胰腺癌中的低表达又提示其可作为抑癌基因发挥作用。本文旨从SIRT7的基因组组成、作用底物及相关肿瘤作用机制等方面阐述SIRT7的研究进展,而其致癌或抑癌作用有可能使其成为肿瘤治疗的新靶点。

Sirtuins are a highly conserved family of nicotinamide adenine dinucleotide （NAD＋）-dependent protein lysine modifying enzymes with deacetylase activity. Mammals have seven sirtuins, namely SIRT1-SIRT7. As a member of the sirtuin family of proteins, SIRT7 is located in nucleus, and it is a highly specific H3K18Ac （acetylated lysine 18 of histone H3） deacetylase. The substrates of SIRT7 include the histone and non-histone proteins. It means that SIRT7 is involved in many cellular activities, such as cell proliferation, cell metabolism, DNA damage and stress, and is closely related to the development of tumor. SIKT7 has been found to be up-regulated in many cancer so far, ixtcluding breast cancer, thyroid cancer, ovarian cancer, cervical cancer, gastric cancer, colorectal cancer and hepatocellular carcinoma, and it may become a novel target for cancer treatment. But the expression of SIRT7 is in lower level in head and neck squamous cell carcinoma and pancreatic cancer suggesting that SIRT7 as a tumor suppressor. In this article, the research progress of SIRT7 is described from the aspects of its genome organization, various substrates, and its related mechanisms in tumorigenesis. The effects of SIRT7 in carcinogenesis and tumor suppression suggest that SIRT7 may be a new target for tumor therapy.