MicroRNA-218 inhibits bladder cancer cell proliferation, migration, and invasion by targeting BMI-1

被引:53
作者
Cheng, Yidong [1 ]
Yang, Xiao [1 ]
Deng, Xiaheng [1 ]
Zhang, Xiaolei [1 ]
Li, Pengchao [1 ]
Tao, Jun [1 ]
Lu, Qiang [1 ]
机构
[1] Nanjing Med Univ, Affiliated Hosp 1, Dept Urol, Nanjing 210029, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
MicroRNA-218; Bladder cancer; BMI-1; Proliferation; Migration; Invasion; AKT PHOSPHORYLATION; LUNG-CANCER; EXPRESSION; PATHWAY; METASTASIS; CARCINOMA; MIR-218; PTEN; PROGRESSION; REPRESSION;
D O I
10.1007/s13277-015-3532-x
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
MicroRNAs (miRNAs) are recognized as important molecules and have emerged as important gene regulators in tumorigenesis. Growing evidence suggested that miR-218 was a tumor suppressor in many human cancers. However, its underlying role in bladder cancer (BCa) remains unclear. The aim of this study was to explore the effect of miR-218 on the proliferation, migration, and invasion of BCa cells. We found that miR-218 was frequently downregulated in BCa tissues compared with normal adjacent tissues. In vitro and in vivo assays demonstrated that miR-218 overexpression in the BCa cells inhibited cell proliferation, migration, and invasion. Luciferase reporter assay showed that BMI-1 was a direct target of miR-218. In addition, we found that miR-218 regulated the expression of BMI-1 and its downstream target (PTEN) and participated in the phosphorylation of AKT. Our findings indicate that miR-218 functions as tumor suppressor in BCa, and the miR-218/BMI-1 axis may provide novel diagnostic and therapeutic strategies for the treatment of BCa.
引用
收藏
页码:8015 / 8023
页数:9
相关论文
共 31 条
[21]   The present and future burden of urinary bladder cancer in the world [J].
Ploeg, Martine ;
Aben, Katja K. H. ;
Kiemeney, Lambertus A. .
WORLD JOURNAL OF UROLOGY, 2009, 27 (03) :289-293
[22]   MicroRNA-218 inhibits the proliferation of human choriocarcinoma JEG-3 cell line by targeting Fbxw8 [J].
Shi, Dazun ;
Tan, Zhihui ;
Lu, Rong ;
Yang, Wenqing ;
Zhang, Yi .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2014, 450 (04) :1241-1246
[23]   The polycomb group protein Bmi-1 represses the tumor suppressor PTEN and induces epithelial-mesenchymal transition in human nasopharyngeal epithelial cells [J].
Song, Li-Bing ;
Li, Jun ;
Liao, Wen-Ting ;
Feng, Yan ;
Yu, Chun-Ping ;
Hu, Li-Juan ;
Kong, Qing-Li ;
Xu, Li-Hua ;
Zhang, Xing ;
Liu, Wan-Li ;
Li, Man-Zhi ;
Zhang, Ling ;
Kang, Tie-Bang ;
Fu, Li-Wu ;
Huang, Wen-Lin ;
Xia, Yun-Fei ;
Tsao, Sai Wah ;
Li, Mengfeng ;
Band, Vimla ;
Band, Hamid ;
Shi, Qing-Hua ;
Zeng, Yi-Xin ;
Zeng, Mu-Sheng .
JOURNAL OF CLINICAL INVESTIGATION, 2009, 119 (12) :3626-3636
[24]   miR-218 on the genomic loss region of chromosome 4p15.31 functions as a tumor suppressor in bladder cancer [J].
Tatarano, Shuichi ;
Chiyomaru, Takeshi ;
Kawakami, Kazumori ;
Enokida, Hideki ;
Yoshino, Hirofumi ;
Hidaka, Hideo ;
Yamasaki, Takeshi ;
Kawahara, Kazuya ;
Nishiyama, Kenryu ;
Seki, Naohiko ;
Nakagawa, Masayuki .
INTERNATIONAL JOURNAL OF ONCOLOGY, 2011, 39 (01) :13-21
[25]   MiR-218 Inhibits Invasion and Metastasis of Gastric Cancer by Targeting the Robo1 Receptor [J].
Tie, Jun ;
Pan, Yanglin ;
Zhao, Lina ;
Wu, Kaichun ;
Liu, Jie ;
Sun, Shiren ;
Guo, Xuegang ;
Wang, Biaoluo ;
Gang, Yi ;
Zhang, Yongguo ;
Li, Quanjiang ;
Qiao, Taidong ;
Zhao, Qingchuan ;
Nie, Yongzhan ;
Fan, Daiming .
PLOS GENETICS, 2010, 6 (03)
[26]   MicroRNA-218 Inhibits Glioma Invasion, Migration, Proliferation, and Cancer Stem-like Cell Self-Renewal by Targeting the Polycomb Group Gene Bmi1 [J].
Tu, Yanyang ;
Gao, Xingchun ;
Li, Gang ;
Fu, Hualin ;
Cui, Daxiang ;
Liu, Hui ;
Jin, Weilin ;
Zhang, Yongsheng .
CANCER RESEARCH, 2013, 73 (19) :6046-6055
[27]   The Tumor Suppressive MicroRNA miR-218 Targets the mTOR Component Rictor and Inhibits AKT Phosphorylation in Oral Cancer [J].
Uesugi, Atsushi ;
Kozaki, Ken-ichi ;
Tsuruta, Tomohiko ;
Furuta, Mayuko ;
Morita, Kei-ichi ;
Imoto, Issei ;
Omura, Ken ;
Inazawa, Johji .
CANCER RESEARCH, 2011, 71 (17) :5765-5778
[28]   Knockdown of the Bmi-1 oncogene inhibits cell proliferation and induces cell apoptosis and is involved in the decrease of Akt phosphorylation in the human breast carcinoma cell line MCF-7 [J].
Xu, Zhengshun ;
Liu, Hongtao ;
Lv, Xinquan ;
Liu, Yuqiong ;
Li, Shenglei ;
Li, Huixiang .
ONCOLOGY REPORTS, 2011, 25 (02) :409-418
[29]   MicroRNA-218 Inhibits Cell Migration and Invasion in Renal Cell Carcinoma through Targeting Caveolin-2 Involved in Focal Adhesion Pathway [J].
Yamasaki, Takeshi ;
Seki, Naohiko ;
Yoshino, Hirofumi ;
Itesako, Toshihiko ;
Hidaka, Hideo ;
Yamada, Yasutoshi ;
Tatarano, Shuichi ;
Yonezawa, Tomokazu ;
Kinoshita, Takashi ;
Nakagawa, Masayuki ;
Enokida, Hideki .
JOURNAL OF UROLOGY, 2013, 190 (03) :1059-1068
[30]  
Yang X, 2014, TUMOUR BIOL J INT SO, DOI [10.1007/s13277-014-2617-2, DOI 10.1007/S13277014-2617-2]