MicroRNA-145 targets vascular endothelial growth factor and inhibits invasion and metastasis of osteosarcoma cells

被引:88
作者
Fan, Lei [1 ]
Wu, Qiang [1 ]
Xing, Xiaojuan [2 ]
Wei, Yulong [1 ]
Shao, Zengwu [1 ]
机构
[1] Huazhong Univ Sci & Technol, Dept Orthopaed, Union Hosp, Tongji Med Coll, Wuhan 430022, Peoples R China
[2] SE Forens Sci Serv, Nanjing 210000, Jiangsu, Peoples R China
关键词
miR-145; vascular endothelial growth factor; osteosarcoma; invasion; metastasis; EXPRESSION; VEGF; CANCER; ISOFORM;
D O I
10.1093/abbs/gms019
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
MicroRNAs are important gene regulators that play a profound role in tumorigenesis. MicroRNA-145 (miR-145), an important member in the family of microRNAs, is under-expressed in several types of tumors and acts as a tumor suppressor. The role and probable pathways of miR-145 in osteosarcoma carcinogenesis are still unknown. In this study, we found that miR-145 was significantly under-expressed in osteosarcoma tissues, and the over-expression of miR-145 could inhibit invasion and angiopoiesis of osteosarcoma cells. Furthermore, the results showed that vascular endothelial growth factor (VEGF) expression was down-regulated in osteosarcoma cells after miR-145 transfection. On the basis of these results, we performed the luciferase assay and verified that miR-145 could down-regulate VEGF at the translational level by partially binding to VEGF 3 untranslated region (3UTR). Therefore, it can be concluded that miR-145 can inhibit invasion and metastasis of osteosarcoma cells. One of the mechanisms is the down-regulation of VEGF expression by miR-145 by binding to the 3UTR of VEGF mRNA specifically. These novel findings may have extensive implications for an effective gene therapy of osteosarcoma.
引用
收藏
页码:407 / 414
页数:8
相关论文
共 31 条
[1]
Akao Y, 2006, ONCOL REP, V16, P845
[2]
The endothelial cell tube formation assay on basement membrane turns 20: state of the science and the art [J].
Arnaoutova, Irina ;
George, Jay ;
Kleinman, Hynda K. ;
Benton, Gabriel .
ANGIOGENESIS, 2009, 12 (03) :267-274
[3]
MicroRNAs: Genomics, biogenesis, mechanism, and function (Reprinted from Cell, vol 116, pg 281-297, 2004) [J].
Bartel, David P. .
CELL, 2007, 131 (04) :11-29
[4]
Principles of MicroRNA-target recognition [J].
Brennecke, J ;
Stark, A ;
Russell, RB ;
Cohen, SM .
PLOS BIOLOGY, 2005, 3 (03) :404-418
[5]
MicroRNA145 Targets BNIP3 and Suppresses Prostate Cancer Progression [J].
Chen, Xueqin ;
Gong, Jing ;
Zeng, Hao ;
Chen, Ni ;
Huang, Rui ;
Huang, Ying ;
Nie, Ling ;
Xu, Miao ;
Xia, Juan ;
Zhao, Fang ;
Meng, Wentong ;
Zhou, Qiao .
CANCER RESEARCH, 2010, 70 (07) :2728-2738
[6]
MicroRNA-145, a Novel Smooth Muscle Cell Phenotypic Marker and Modulator, Controls Vascular Neointimal Lesion Formation [J].
Cheng, Yunhui ;
Liu, Xiaojun ;
Yang, Jian ;
Lin, Ying ;
Xu, Da-Zhong ;
Lu, Qi ;
Deitch, Edwin A. ;
Huo, Yuqing ;
Delphin, Ellise S. ;
Zhang, Chunxiang .
CIRCULATION RESEARCH, 2009, 105 (02) :158-U113
[7]
Oncomirs - microRNAs with a role in cancer [J].
Esquela-Kerscher, A ;
Slack, FJ .
NATURE REVIEWS CANCER, 2006, 6 (04) :259-269
[8]
MicroRNAs as tumor suppressors [J].
Hammond, Scott M. .
NATURE GENETICS, 2007, 39 (05) :582-583
[9]
Hartford CM, 2006, J PEDIAT HEMATOL ONC, V28, P43
[10]
MiRNA-Directed Regulation of VEGF and Other Angiogenic Factors under Hypoxia [J].
Hua, Zhong ;
Lv, Qing ;
Ye, Wenbin ;
Wong, Chung-Kwun Amy ;
Cai, Guoping ;
Gu, Dayong ;
Ji, Yanhong ;
Zhao, Chen ;
Wang, Jifeng ;
Yang, Burton B. ;
Zhang, Yaou .
PLOS ONE, 2006, 1 (02)