长寿蛋白SIRT6在肿瘤发生发展中的作用

Function of SIRT6 in tumor initiation and progression

摘要:

SIRT6作为组蛋白去乙酰化转移酶 (Histone deacetylases，HDACs) 第三家族长寿蛋白 (Sirtuins，SIRTs) 中的一员，具有多种催化酶活性，且在抗衰老、染色质调节、转录调控、糖脂代谢、DNA损伤修复等生物学过程中起着重要的作用。近年来的证据表明，SIRT6的表达与肿瘤的发生发展密切相关，且在多种肿瘤中起着关键的调节作用，比如肝癌、肺癌、乳腺癌和生殖系统肿瘤等。但是由于SIRT6功能的多样性，及其上下游信号通路的复杂性，SIRT6在肿瘤中可能扮演着双重角色。在大多数情况下，SIRT6扮演着抑癌基因的角色，少数情况下，SIRT6却又发挥着促癌作用。本文结合目前本实验室的研究，阐述了近几年来关于SIRT6在多种肿瘤发生及发展中的最新发现，总结了其作用机制，并对其研究及应用前景进行了展望。

Abstract:

As a member of the sirtuins family, also called Class III histone deacetylases (HDACs), SIRT6 has many catalytic enzyme activities and plays a pivotal role in biological processes including anti-aging, chromatin regulation, transcriptional control, glucose and lipid metabolism, and DNA damage repair. Recently, increasing evidences indicated that SIRT6 was related to initiation and development of tumors, such as hepatic cancer, lung cancer, breast cancer and genital system tumors. However, SIRT6 might play a dual role in tumorigenesis and progression. SIRT6 often acted as a tumor suppressor, but might play an oncogenic role. Based on our current study, we depicted the essential roles of SIRT6 in the initiation and progression of various tumors, and summarized its mode of actions, which might provide clues for cancer therapy.