近日，国际学术期刊scientific reports在线发表了中国科学家关于组蛋白去乙酰化酶sirt7在胃癌中具体作用的最新科研进展，他们发现sirt7对胃癌发展具有重要促进作用，而这种促癌作用主要是通过sirt7的组蛋白去乙酰化酶功能影响具有抗癌作用的microRNA-34a的表达实现的。

　　胃癌在全球最常见的癌症中排名第四，胃癌病人的5年生存率非常低。之前研究发现表观遗传修饰在胃癌发展中具有重要作用。但目前对组蛋白修饰酶在胃癌中的作用了解较少。

　　研究人员发现sirt7，一种NAD+依赖性组蛋白去乙酰化酶，在人类胃癌组织中具有高表达。Sirt7的表达水平与疾病发展阶段、转移和病人存活具有显著相关性。在胃癌细胞中敲低Sirt7能够抑制细胞增殖过程和体外克隆形成。皮下移植瘤实验同样证明sirt7表达降低能够显著抑制胃癌细胞生长。除此之外，删除Sirt7能够通过上调促凋亡蛋白下调抗凋亡蛋白表达，诱导胃癌细胞凋亡。

　　研究人员对机制进行探究发现，srit7能够结合miR-34a启动子，对H3K18ac进行去乙酰化，抑制miR-34a表达。而在miR-34a缺失之后，通过敲低sirt7诱导的胃癌细胞凋亡也会受到抑制，并且会恢复细胞增殖能力和克隆形成能力。miR-34a的缺失会降低sirt7敲低对胃癌生长的抑制作用。因此，miR-34a与胃癌病人的生存具有紧密相关性，具有重要开发价值。

　　doi:10.1038/srep09787

　　Sirt7 promotes gastric cancer growth and inhibits apoptosis by epigenetically inhibiting miR-34a

　　Shun Zhang,Ping Chen,Zuoan Huang,Xiaorong Hu,Mengting Chen,Shanshan Hu,Yixin Hu &Ting Cai

　　Gastric cancer is the fourth most common cancer worldwide, with a low 5-year survival rate. Epigenetic modification plays pivotal roles in gastric cancer development. However, the role of histone-modifying enzymes in gastric cancer remains largely unknown. Here we report that Sirt7, a NAD+-dependent class III histone deacetylase, is over-expressed in human gastric cancer tissues. Sirt7 level is significantly correlated with disease stage, metastasis, and survival. Knockdown of Sirt7 in gastric cancer cells inhibits cell proliferation and colony formation in vitro. In vivo subcutaneous xenograft results also show that Sirt7 knockdown can markedly repress gastric cancer cell growth. In addition,Sirt7 depletion induces apoptosis in gastric cancer cells via up-regulating expression of pro-apoptotic proteins and down-regulating anti-apoptotic proteins. Mechanically, Sirt7binds to the promoter of miR-34a and deacetylases the H3K18ac, thus represses miR-34a expression. Reversely, depletion of miR-34a inhibits gastric cancer apoptosis induced bySirt7 knockdown, and restores cellular capacity of proliferation and colony formation. miR-34a depletion reduces Sirt7-knockdown-induced arrest of gastric growth. Finally, miR-34a is tightly associated with survival of patients with gastric cancer.