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标题：Sirt7 promotes gastric cancer growth and inhibits apoptosis by epigenetically inhibiting miR-34a
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作者：Shun Zhang ; Ping Chen ; Zuoan Huang 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2015
卷号：5
期号：1
DOI：10.1038/srep09787
语种：English
出版社：Springer Nature
摘要：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. Sirt 7 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, Sirt7 binds 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 by Sirt7 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.