Inhibiting Enhancer of Zeste Homolog 2 Promotes Cellular Senescence in Gastric Cancer Cells SGC-7901 by Activation of p21 and p16

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-independe...