title: EZH2 silencing with RNA interference induces G2/M arrest in human lung cancer cells in vitro.
abstract: Nonsmall-cell lung cancer has a high mortality rate and poor prognosis. In the present study, we silenced EZH2 and explored the consequent cell cycle changes. The expression of cell-cycle-related proteins, including p53, p21, Cdc2, and cyclin B1, was detected with western blotting, and the cell cycle distribution was determined with flow cytometry. Inhibition of EZH2 expression changed the cell cycle distribution, in particular inducing G2/M arrest. Expression of Cdc2 and cyclin B1 was significantly decreased in A549 and HTB-56 cells after EZH2-siRNA treatment. In addition, p53 expression was increased by 21% and 18%, and p21 expression was increased by 31% and 23%, in A549 and HTB-56 cells, respectively, in the presence of EZH2-siRNA. This study clearly demonstrates that modulation of EZH2 expression with siRNA affects the cell cycle and the expression levels of p53 and p21, thereby changing cyclin B1 and Cdc2 expression and inducing G2/M arrest. These results may explain the observed antitumor activity of EZH2 silencing. Such explorations of the molecular mechanism of EZH2 will help us develop novel approaches to the diagnosis, treatment, and prevention of nonsmall-cell lung cancer.
authors.affiliation: Department of Thoracic-Cardio Surgery, First Affiliated Hospital of PLA General Hospital, Beijing 100048, China.
authors.forename: Hui
authors.identifier: 0000-0002-9085-5488
authors.initials: H
authors.lastname: Xia
authors.affiliation: Department of Thoracic-Cardio Surgery, First Affiliated Hospital of PLA General Hospital, Beijing 100048, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Thoracic-Cardio Surgery, First Affiliated Hospital of PLA General Hospital, Beijing 100048, China.
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Thoracic-Cardio Surgery, First Affiliated Hospital of PLA General Hospital, Beijing 100048, China.
authors.forename: Nannan
authors.initials: N
authors.lastname: Guo
authors.affiliation: Department of Thoracic-Cardio Surgery, First Affiliated Hospital of PLA General Hospital, Beijing 100048, China.
authors.forename: Changhai
authors.identifier: 0000-0001-9177-5458
authors.initials: C
authors.lastname: Yu
mesh_terms: D017209:Apoptosis / Q000235:genetics; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics*; D045744:Cell Line, Tumor; D000071221:Enhancer of Zeste Homolog 2 Protein; D020868:Gene Silencing / Q000187:drug effects*; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D063151:Polycomb Repressive Complex 2 / Q000235:genetics*; D012313:RNA / Q000008:administration & dosage / Q000235:genetics*; D034622:RNA Interference; D016896:Treatment Outcome
chemical_list: D012313:RNA; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2
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