Let-7a inhibits proliferation and induces apoptosis by targeting EZH2 in nasopharyngeal carcinoma cells

被引:39
作者
Cai, Kemin [1 ]
Wan, Yi [2 ]
Sun, Guan [3 ]
Shi, Lei [4 ]
Bao, Xueli [1 ]
Wang, Zhimin [2 ]
机构
[1] Taizhou Peoples Hosp, Dept Otorhinolaryngol Head & Neck Surg, Taizhou 225300, Jiangsu, Peoples R China
[2] Shanghai Jiao Tong Univ, Sch Med, Suzhou Kowloon Hosp, Dept Neurosurg, Suzhou 215021, Peoples R China
[3] Nantong Univ, Affiliated Yancheng Hosp 4, Dept Neurosurg, Yancheng 224000, Peoples R China
[4] Jiangsu Univ, Peoples Hosp Kunshan 1, Dept Neurosurg, Suzhou 215300, Peoples R China
关键词
let-7a; enhancer of zeste homolog 2; proliferation; apoptosis; nasopharyngeal carcinoma; TUMOR-SUPPRESSOR; EXPRESSION; COMPLEX; CANCER; AGGRESSIVENESS; TUMORIGENESIS; ONTOLOGY; MIR-26A; PROTEIN; ROLES;
D O I
10.3892/or.2012.2027
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Let-7a is frequently downregulated in various types of human cancer including nasopharyngeal carcinoma. However, the underlying mechanism of let-7a action in nasopharyngeal carcinoma remains elusive. In this study, we show that the enhancer of zeste homolog 2 (EZH2) is a direct target of let-7a in human nasopharyngeal carcinoma cells. The inhibition of EZH2 in vitro by let-7a, EZH2 si RNA, attenuated nasopharyngeal carcinoma cell growth, inhibited cell proliferation and induced cell apoptosis. In addition, for each biological process we identified ontology-associated transcripts that significantly correlate with EZH2 expression. Finally, the expression of EZH2 significantly abrogated let-7a-mediated cell proliferation and apoptosis in the nasopharyngeal carcinoma cells. Taken together, our results suggest that let-7a and EZH2 may be potential therapeutic targets for nasopharyngeal carcinoma.
引用
收藏
页码:2101 / 2106
页数:6
相关论文
共 28 条
[1]   Enhancer of Zeste homolog 2 (EZH2) is overexpressed in recurrent nasopharyngeal carcinoma and is regulated by miR-26a, miR-101, and miR-98 [J].
Alajez, N. M. ;
Shi, W. ;
Hui, A. B. Y. ;
Bruce, J. ;
Lenarduzzi, M. ;
Ito, E. ;
Yue, S. ;
O'Sullivan, B. ;
Liu, F-F .
CELL DEATH & DISEASE, 2010, 1 :e85-e85
[2]   Gene Ontology: tool for the unification of biology [J].
Ashburner, M ;
Ball, CA ;
Blake, JA ;
Botstein, D ;
Butler, H ;
Cherry, JM ;
Davis, AP ;
Dolinski, K ;
Dwight, SS ;
Eppig, JT ;
Harris, MA ;
Hill, DP ;
Issel-Tarver, L ;
Kasarskis, A ;
Lewis, S ;
Matese, JC ;
Richardson, JE ;
Ringwald, M ;
Rubin, GM ;
Sherlock, G .
NATURE GENETICS, 2000, 25 (01) :25-29
[3]   AmiGO: online access to ontology and annotation data [J].
Carbon, Seth ;
Ireland, Amelia ;
Mungall, Christopher J. ;
Shu, ShengQiang ;
Marshall, Brad ;
Lewis, Suzanna .
BIOINFORMATICS, 2009, 25 (02) :288-289
[4]   The role of EZH2 in tumour progression [J].
Chang, C-J ;
Hung, M-C .
BRITISH JOURNAL OF CANCER, 2012, 106 (02) :243-247
[5]   HDAC6 Regulates Mitochondrial Transport in Hippocampal Neurons [J].
Chen, Sigeng ;
Owens, Geoffrey C. ;
Makarenkova, Helen ;
Edelman, David B. .
PLOS ONE, 2010, 5 (05)
[6]   Enhancer of zeste homolog 2 is a novel prognostic biomarker in nonsmall cell lung cancer [J].
Huqun ;
Ishikawa, Rinako ;
Zhang, Jialing ;
Miyazawa, Hitoshi ;
Goto, Yoshiya ;
Shimizu, Yoshihiko ;
Hagiwara, Koichi ;
Koyama, Nobuyuki .
CANCER, 2012, 118 (06) :1599-1606
[7]   ENHANCER OF ZESTE HOMOLOG 2 OVEREXPRESSION IN NASOPHARYNGEAL CARCINOMA: AN INDEPENDENT POOR PROGNOSTICATOR THAT ENHANCES CELL GROWTH [J].
Hwang, Chung-Feng ;
Huang, Hsuan-Ying ;
Chen, Chang-Han ;
Chien, Chih-Yen ;
Hsu, Yao-Chung ;
Li, Chien-Feng ;
Fang, Fu-Min .
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 2012, 82 (02) :597-604
[8]   Mir-214-Dependent Regulation of the Polycomb Protein Ezh2 in Skeletal Muscle and Embryonic Stem Cells [J].
Juan, Aster H. ;
Kumar, Roshan M. ;
Marx, Joseph G. ;
Young, Richard A. ;
Sartorelli, Vittorio .
MOLECULAR CELL, 2009, 36 (01) :61-74
[9]   MicroRNA let-7a suppresses breast cancer cell migration and invasion through downregulation of C-C chemokine receptor type 7 [J].
Kim, Seok-Jun ;
Shin, Ji-Young ;
Lee, Kang-Duck ;
Bae, Young-Ki ;
Sung, Ki Woong ;
Nam, Seok Jin ;
Chun, Kyung-Hee .
BREAST CANCER RESEARCH, 2012, 14 (01)
[10]   microRNA expression profiling of nasopharyngeal carcinoma [J].
Li, Ting ;
Chen, Jia-Xin ;
Fu, Xu-Ping ;
Yang, Shu ;
Zhang, Zheng ;
Chen, Kh-He ;
Li, Yao .
ONCOLOGY REPORTS, 2011, 25 (05) :1353-1363