MiR-205 determines the radioresistance of human nasopharyngeal carcinoma by directly targeting PTEN

被引:184
作者
Qu, Changju [1 ]
Liang, Zhihui [2 ]
Huang, JiaLing [3 ]
Zhao, Ruiying [1 ]
Su, Chunhui [1 ]
Wang, Sumei
Wang, Xudan
Zhang, Rong [2 ]
Lee, Mong-Hong [1 ]
Yang, Huiling
机构
[1] Univ Texas MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX 77030 USA
[2] Sun Yat Sen Univ, State Key Lab Oncol S China, Guangzhou 510275, Guangdong, Peoples R China
[3] Univ Penn, Div Infect Dis, Philadelphia, PA 19104 USA
基金
中国国家自然科学基金;
关键词
nasopharyngeal carcinoma; PTEN; miRNA; miR-205; radioresistance; LUNG-CANCER CELLS; DOWN-REGULATION; BREAST-CANCER; MESENCHYMAL TRANSITION; DRUG-RESISTANCE; OVARIAN-CANCER; EXPRESSION; RADIATION; MICRORNA; APOPTOSIS;
D O I
10.4161/cc.11.4.19228
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Radiotherapy is the primary treatment for nasopharyngeal carcinoma (NPC), but radioresistance severely reduces NPC radiocurability. Here, we have established a radio-resistant NPC cell line, CNE-2R, and investigate the role of miRNAs in radioresistance. The miRNAs microarray assay reveals that miRNAs are differentially expressed between CNE-2R and its parental cell line CNE-2. We find that miR-205 is elevated in CNE-2R. A target prediction algorithm suggests that miR-205 regulates expression of PTEN, a tumor-suppressor. Introducing miR-205 into CNE-2 cells suppresses PTEN protein expression, followed by activation of AKT, increased number of foci formation and reduction of cell apoptosis postirradiation. On the other hand, knocking down miR-205 in CNE-2R cells compromises the inhibition of PTEN and increases cell apoptosis. Significantly, immunohistochemistry studies demonstrate that PTEN is downregulated at late stages of NPC, and that miR-205 is significantly elevated followed the radiotherapy. Our data conclude that miR-205 contributes to radioresistance of NPC by directly targeting PTEN. Both miR-205 and PTEN are potential predictive biomarkers for radiosensitivity of NPC and may serve as targets for achieve successful radiotherapy in NPC.
引用
收藏
页码:785 / 796
页数:12
相关论文
共 36 条
  • [1] miR-218 Suppresses Nasopharyngeal Cancer Progression through Downregulation of Survivin and the SLIT2-ROBO1 Pathway
    Alajez, Nehad M.
    Lenarduzzi, Michelle
    Ito, Emma
    Hui, Angela B. Y.
    Shi, Wei
    Bruce, Jeff
    Yue, Shijun
    Huang, Shao H.
    Xu, Wei
    Waldron, John
    O'Sullivan, Brian
    Liu, Fei-Fei
    [J]. CANCER RESEARCH, 2011, 71 (06) : 2381 - 2391
  • [2] Chang JTC, 2004, J FORMOS MED ASSOC, V103, P496
  • [3] Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Inhibitors: Rationale and Importance to Inhibiting These Pathways in Human Health
    Chappell, William H.
    Steelman, Linda S.
    Long, Jacquelyn M.
    Kempf, Ruth C.
    Abrams, Stephen L.
    Franklin, Richard A.
    Baesecke, Joerg
    Stivala, Franca
    Donia, Marco
    Fagone, Paolo
    Malaponte, Graziella
    Mazzarino, Maria C.
    Nicoletti, Ferdinando
    Libra, Massimo
    Maksimovic-Ivanic, Danijela
    Mijatovic, Sanja
    Montalto, Giuseppe
    Cervello, Melchiorre
    Laidler, Piotr
    Milella, Michele
    Tafuri, Agostino
    Bonati, Antonio
    Evangelisti, Camilla
    Cocco, Lucio
    Martelli, Alberto M.
    McCubrey, James A.
    [J]. ONCOTARGET, 2011, 2 (03) : 135 - 164
  • [4] Cheng Jin-Jian, 2006, Ai Zheng, V25, P45
  • [5] Nasopharyngeal carcinoma treated with external radiotherapy, brachytherapy, and concurrent/adjuvant chemotherapy
    DeNittis, AS
    Liu, L
    Rosenthal, DI
    Machtay, M
    [J]. AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS, 2002, 25 (01): : 93 - 95
  • [6] Identification of Biomarkers for Predicting Nasopharyngeal Carcinoma Response to Radiotherapy by Proteomics
    Feng, Xue-Ping
    Yi, Hong
    Li, Mao-Yu
    Li, Xin-Hui
    Yi, Bin
    Zhang, Peng-Fei
    Li, Cui
    Peng, Fang
    Tang, Can-E
    Li, Jian-Ling
    Chen, Zhu-Chu
    Xiao, Zhi-Qiang
    [J]. CANCER RESEARCH, 2010, 70 (09) : 3450 - 3462
  • [7] miR-205 Exerts Tumor-Suppressive Functions in Human Prostate through Down-regulation of Protein Kinase Cε
    Gandellini, Paolo
    Folini, Marco
    Longoni, Nicole
    Pennati, Marzia
    Binda, Mara
    Colecchia, Maurizio
    Salvioni, Roberto
    Supino, Rosanna
    Moretti, Roberta
    Limonta, Patrizia
    Valdagni, Riccardo
    Daidone, Maria Grazia
    Zaffaroni, Nadia
    [J]. CANCER RESEARCH, 2009, 69 (06) : 2287 - 2295
  • [8] MicroRNAs as regulators of epithelial-mesenchymal transition
    Gregory, Philip. A.
    Bracken, Cameron P.
    Bert, Andrew G.
    Goodall, Gregory J.
    [J]. CELL CYCLE, 2008, 7 (20) : 3112 - 3117
  • [9] The mir-200 family and mir-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1
    Gregory, Philip A.
    Bert, Andrew G.
    Paterson, Emily L.
    Barry, Simon C.
    Tsykin, Anna
    Farshid, Gelareh
    Vadas, Mathew A.
    Khew-Goodall, Yeesim
    Goodall, Gregory J.
    [J]. NATURE CELL BIOLOGY, 2008, 10 (05) : 593 - 601
  • [10] The expression of p63 is associated with the differential stage in nasopharyngeal carcinoma and EBV infection
    Guo, Can
    Pan, Zhi-Gang
    Li, Da-Jiang
    Yun, Jing-Ping
    Zheng, Mei-Zhen
    Hu, Zhe-Yu
    Cheng, Li-Zhen
    Zeng, Yi-Xin
    [J]. JOURNAL OF TRANSLATIONAL MEDICINE, 2006, 4 (1)