title: Sirt7 promotes gastric cancer growth and inhibits apoptosis by epigenetically inhibiting miR-34a.
abstract: 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, 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.
authors: Stem Cell Laboratory, Ningbo No.2 Hospital, Ningbo 315010, Zhejiang, China.
authors: Shun
authors: S
authors: Zhang
authors: Gastrointestinal and Hernia Ward, Ningbo No.2 Hospital, Ningbo 315010, Zhejiang, China.
authors: Ping
authors: P
authors: Chen
authors: Stem Cell Laboratory, Ningbo No.2 Hospital, Ningbo 315010, Zhejiang, China.
authors: Zuoan
authors: Z
authors: Huang
authors: Stem Cell Laboratory, Ningbo No.2 Hospital, Ningbo 315010, Zhejiang, China.
authors: Xiaorong
authors: X
authors: Hu
authors: Department of Internal Medicine, School of Medicine, Ningbo University, Ningbo 315211, Zhejiang, China.
authors: Mengting
authors: M
authors: Chen
authors: Department of Internal Medicine, School of Medicine, Ningbo University, Ningbo 315211, Zhejiang, China.
authors: Shanshan
authors: S
authors: Hu
authors: Department of Internal Medicine, School of Medicine, Ningbo University, Ningbo 315211, Zhejiang, China.
authors: Yixin
authors: Y
authors: Hu
authors: Stem Cell Laboratory, Ningbo No.2 Hospital, Ningbo 315010, Zhejiang, China.
authors: Ting
authors: T
authors: Cai
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics*; D045744:Cell Line, Tumor; D044127:Epigenesis, Genetic; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D037761:Sirtuins / Q000235:genetics* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D016896:Treatment Outcome; D047368:Tumor Burden
chemical_list: C522425:MIRN34 microRNA, human; D035683:MicroRNAs; C510661:SIRT7 protein, human; D037761:Sirtuins