title: Inhibiting enhancer of zeste homolog 2 promotes cellular senescence in gastric cancer cells SGC-7901 by activation of p21 and p16.
abstract: Cellular senescence, which can be defined as a stress response preventing the propagation of cells that have accumulated potentially oncogenic alterations, is invariably associated with a permanent cell cycle arrest. Enhancer of zeste homolog 2 (EZH2) as a member of polycomb group proteins and its targets include cell cycle regulatory proteins, which govern cell cycle progression and cellular senescence. In this study, we report that EZH2 depletion promotes the senescent state in human gastric cancer cells SGC-7901. We found that EZH2 functionally suppressed the senescent state in human gastric cancer cells SGC-7901. EZH2 depletion inhibited cell proliferation, arrested cellular cycle, restored features of a cellular senescence phenotype, and promoted doxorubicin-induced senescence. To prove that EZH2 expression contributes substantially to the change of key cell cycle regulators, we showed that p21 and p16 were activated to a certain extent upon EZH2 depletion and activation of p21 was in a p53-independent manner. Taken together, our data suggest that EZH2 depletion promotes the progression of senescence by mediating the activation of tumor suppressor genes p21 and p16, and could serve as a potential epigenetic target for gastric cancer therapy.
authors.affiliation: Department of Gastrointestinal Surgery II, Wuhan Union Hospital, Tongji Medical College of Huazhong University of Science and Technology , Wuhan, Hubei Province, People's Republic of China .
authors.forename: Jie
authors.initials: J
authors.lastname: Bai
authors.forename: Junhua
authors.initials: J
authors.lastname: Chen
authors.forename: Muyuan
authors.initials: M
authors.lastname: Ma
authors.forename: Ming
authors.initials: M
authors.lastname: Cai
authors.forename: Fei
authors.initials: F
authors.lastname: Xu
authors.forename: Guobin
authors.initials: G
authors.lastname: Wang
authors.forename: Kaixiong
authors.initials: K
authors.lastname: Tao
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Shuai
mesh_terms: D045744:Cell Line, Tumor; D016922:Cellular Senescence; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D004317:Doxorubicin; D000071221:Enhancer of Zeste Homolog 2 Protein; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism*; D063151:Polycomb Repressive Complex 2 / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: C493956:CDKN1A protein, human; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53; D004317:Doxorubicin; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2