组蛋白乙酰化是表观遗传学的主要作用方式之一，在多种恶性肿瘤中均存在异常，包括甲状腺癌。Sirtuin家族是一类NAD+（烟酰胺腺嘌呤二核苷酸）依赖的组蛋白去乙酰化酶，包括七个成员（SIRT1-7）。尽管有研究显示SIRT7可通过引起H3K18去乙酰化，导致多个抑癌基因的转录失活，但其在恶性肿瘤发生中的作用机制特别是甲状腺癌尚不明确。我们的前期结果显示SIRT7在甲状腺癌中的表达明显高于癌旁组织，且敲减其表达能显著抑制肿瘤细胞的增殖、克隆形成、迁移和侵袭能力并诱导肿瘤细胞发生周期阻滞及凋亡；相反，过表达SIRT7则促进肿瘤细胞的增殖和侵袭能力。此外，我们还发现SIRT7可以调控PI3K/Akt/mTOR/S6K1信号通路的活性。基于此，本项目拟从表观遗传学调控及蛋白质之间相互作用两方面阐明SIRT7在甲状腺癌发生及发展中的具体分子机制，绘制其基因调控网络，为甲状腺癌的治疗提供新的靶点和思路。

Histone acetylation is a major form of epigenetic modification catalyzed by histone acetyl transferase (HATs) and deacetylase. Sirtuin family is a type of enzymes with nicotinamide adenine dinucleotide (NAD)-dependent protein lysine deacylase function, which comprises seven members in humans (SIRT1-7) and plays a critical role in tumorigenesis. The previous study has demonstrated that SIRT7 can cause a decreased expression of a panel of tumor suppressor genes, contributing to tumorigenesis through deacetylating H3K18Ac and promoting transcriptional repression. However, its role and mechanism in human cancers particularly in thyroid cancer remain largely unclear. Our preliminary data showed that SIRT7 expression was significantly down-regulated in thyroid cancer tissues as compared with matched non-cancerous thyroid tissues. Knockdown of SIRT7 in thyroid cancer cells dramatically inhibited cell proliferation, colony formation, migration and invasion, induced cell cycle arrest and apoptosis. On the other hand, ectopic SIRT7 expression promoted thyroid cancer cell growth and invasiveness. Importantly, we found that SIRT7 promoted thyroid tumorigenesis through activating the PI3K/Akt/mTOR/S6K1 cascade. Thus, the aims of this project are to further explore biological roles and molecular mechanisms of SIRT7 in thyroid tumorigenesis at epigenetic regulation and protein-protein interaction levels, and identify its downstream target genes using ChIP-Seq and RNA-Seq approaches.