Inhibitory Effects of MicroRNA-34a on Cell Migration and Invasion of Invasive Urothelial Bladder Carcinoma by Targeting Notch1

被引:45
|
作者
Zhang, Chao [1 ,3 ]
Yao, Zhiyong [4 ]
Zhu, Mingyang [1 ]
Ma, Xin [1 ]
Shi, Taoping [1 ]
Li, Hongzhao [1 ]
Wang, Baojun [1 ]
Ouyang, Jinzhi [2 ]
Zhang, Xu [1 ]
机构
[1] Chinese Peoples Liberat Army Gen Hosp, Dept Urol, Beijing 100853, Peoples R China
[2] Chinese Peoples Liberat Army Gen Hosp, Dept Endocrinol, Beijing 100853, Peoples R China
[3] Nankai Univ, Tianjin 300071, Peoples R China
[4] Air Force Gen Hosp PLA, Dept Urol, Beijing 1000853, Peoples R China
基金
中国国家自然科学基金;
关键词
microRNA-34a; urothelial carcinoma; migration; invasion; Notch1; DOWN-REGULATION; PANCREATIC-CANCER; KEY MEDIATOR; BETA-CATENIN; STEM-CELLS; PROLIFERATION; EXPRESSION; GROWTH; MATRIX-METALLOPROTEINASE-9; ACTIVATION;
D O I
10.1007/s11596-012-0065-z
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
MicroRNAs (miRNAs or miRs) are a class of short, non-coding RNAs that participate in various oncological processes. This study aims to explore the roles of microRNA-34a (miR-34a) in invasive urothelial bladder carcinoma. miR-34a was transfected into bladder cancer cell lines 253J and J82. The miR-34a expression levels in tissues and cells were detected by using qRT-PCR. The Notch1 expression was detected by qRT-PCR and Western blotting. Cell migratory and invasive abilities were measured by Transwell chamber assay. Bioinformatics and luciferase assay were performed to predict and analyze the binding sites between miRNA-34a and Notch1. It was found that there was aberrant expression of miR-34a in bladder cancer tissues. Moreover, we revealed that ectopic expression of miR-34a suppressed cell migration and invasion, while forced expression of Notch1 increased cell migratory and invasive abilities. Finally, we observed that miR-34a transfection significantly down-regulated luciferase activity and reduced the mRNA and protein levels of Notch1. Our study concluded that microRNA-34a antagonizes Notch1 and inhibits cell migration and invasion of bladder cancer cells, which indicates the tumor-suppressive function of microRNA-34a in bladder cancer.
引用
收藏
页码:375 / 382
页数:8
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