EZH2 Silencing with RNA Interference Induces G2/M Arrest in Human Lung Cancer Cells In Vitro

被引:13
作者
Xia, Hui [1 ]
Zhang, Wen [1 ]
Li, Yingjie [1 ]
Guo, Nannan [1 ]
Yu, Changhai [1 ]
机构
[1] Peoples Liberat Army Gen Hosp, Affiliated Hosp 1, Dept Thorac Cardio Surg, Beijing 100048, Peoples R China
关键词
CYCLE ARREST; P53; CHECKPOINT; EXPRESSION; INHIBITION; APOPTOSIS; RECEPTOR; PATHWAY; DOWNSTREAM; ABROGATION;
D O I
10.1155/2014/348728
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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 G(2)/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 G(2)/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.
引用
收藏
页数:8
相关论文
共 36 条
[1]   Involvement of the interaction between p21 and proliferating cell nuclear antigen for the maintenance of G2/M arrest after DNA damage [J].
Ando, T ;
Kawabe, T ;
Ohara, H ;
Ducommun, B ;
Itoh, M ;
Okamoto, T .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (46) :42971-42977
[2]   EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer [J].
Adrian P. Bracken ;
Diego Pasini ;
Maria Capra ;
Elena Prosperini ;
Elena Colli ;
Kristian Helin .
The EMBO Journal, 2003, 22 (20) :5323-5335
[3]   Poorly differentiated synovial sarcoma is associated with high expression of enhancer of zeste homologue 2 (EZH2) [J].
Changchien, Yi-Che ;
Tatrai, Peter ;
Papp, Gergo ;
Sapi, Johanna ;
Fonyad, Laszlo ;
Szendroi, Miklos ;
Papai, Zsuzsanna ;
Sapi, Zoltan .
JOURNAL OF TRANSLATIONAL MEDICINE, 2012, 10
[4]   Induction of Fas-mediated extrinsic apoptosis, p21WAF1-related G2/M cell cycle arrest and ROS generation by costunolide in estrogen receptor-negative breast cancer cells, MDA-MB-231 [J].
Choi, Youn Kyung ;
Seo, Hye Sook ;
Choi, Han Seok ;
Choi, Hyeong Sim ;
Kim, Soon Re ;
Shin, Yong Cheol ;
Ko, Seong-Gyu .
MOLECULAR AND CELLULAR BIOCHEMISTRY, 2012, 363 (1-2) :119-128
[5]   Physical Interaction between MYCN Oncogene and Polycomb Repressive Complex 2 (PRC2) in Neuroblastoma FUNCTIONAL AND THERAPEUTIC IMPLICATIONS [J].
Corvetta, Daisy ;
Chayka, Olesya ;
Gherardi, Samuele ;
D'Acunto, Cosimo W. ;
Cantilena, Sandra ;
Valli, Emanuele ;
Piotrowska, Izabela ;
Perini, Giovanni ;
Sala, Arturo .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2013, 288 (12) :8332-8341
[6]   Understanding the limitations of radiation-induced cell cycle checkpoints [J].
Deckbar, Dorothee ;
Jeggo, Penny A. ;
Loebrich, Markus .
CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY, 2011, 46 (04) :271-283
[7]   Strategies for Prolonged Therapy in Patients With Advanced Non-Small-Cell Lung Cancer [J].
Fidias, Panos ;
Novello, Silvia .
JOURNAL OF CLINICAL ONCOLOGY, 2010, 28 (34) :5116-5123
[8]   Pemetrexed in advanced non-small-cell lung cancer [J].
Fuld, Alexander D. ;
Dragnev, Konstantin H. ;
Rigas, James R. .
EXPERT OPINION ON PHARMACOTHERAPY, 2010, 11 (08) :1387-1402
[9]   Downregulation of EZH2 decreases growth of estrogen receptor-negative invasive breast carcinoma and requires BRCA1 [J].
Gonzalez, M. E. ;
Li, X. ;
Toy, K. ;
DuPrie, M. ;
Ventura, A. C. ;
Banerjee, M. ;
Ljungman, M. ;
Merajver, S. D. ;
Kleer, C. G. .
ONCOGENE, 2009, 28 (06) :843-853
[10]   P53 is a NF-Y- and p21-independent, Sp1-dependent repressor of cyclin B1 transcription [J].
Innocente, SA ;
Lee, JM .
FEBS LETTERS, 2005, 579 (05) :1001-1007