microRNA-194 suppresses osteosarcoma cell proliferation and metastasis in vitro and in vivo by targeting CDH2 and IGF1R

被引:79
|
作者
Han, Kang [1 ,2 ]
Zhao, Tingbao [2 ]
Chen, Xiang [3 ]
Bian, Na [1 ]
Yang, Tongtao [1 ]
Ma, Qiong [1 ]
Cai, Chengkui [1 ]
Fan, Qingyu [1 ]
Zhou, Yong [1 ]
Ma, Baoan [1 ]
机构
[1] Fourth Mil Med Univ, Dept Orthoped Surg, Orthoped Oncol Inst Chinese PLA, Tangdu Hosp, Xian 710032, Shaanxi, Peoples R China
[2] Jinan Mil Area Command Chinese PLA, Dept Spinal Cord Injury, Gen Hosp, Jinan, Shandong, Peoples R China
[3] Dept Baylor Coll Med, Houston, TX USA
关键词
osteosarcoma; miR-194; CDH2; IGF1R; metastasis; proliferation; GASTRIC-CANCER; BREAST-CANCER; DOWN-REGULATION; EXPRESSION; DIFFERENTIATION; ACTIVATION; INVASION; ONCOGENE; GENOMICS; SURVIVAL;
D O I
10.3892/ijo.2014.2571
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Studies have shown that miR-194 functions as a tumor suppressor and is associated with tumor growth and metastasis. We studied the effects of miR-194 in osteosarcoma and the possible mechanism by which miR-194 affected the survival, apoptosis and metastasis of osteosarcoma. Both human osteosarcoma cell lines SOSP-9607 and U2-OS were transfected with recombinant lentiviruses to regulate miR-194 expression. Overexpression of miR-194 partially inhibited the proliferation, migration, and invasion of osteosarcoma cells in vitro, as well as tumor growth and pulmonary metastasis of osteosarcoma cells in vivo. Potential miR-194 target genes were predicted using bioinformatics. Luciferase reporter assay, real-time quantitative PCR and western blotting confirmed that CDH2 (N-cadherin) and IGF1R were targets of miR-194. Using real-time quantitative PCR, we evaluated the expression of miR-194 and two miR-194 target genes, CDH2 and IGF1R in osteosarcoma samples from 107 patients and 99 formalin- or paraformalin-fixed paraffin-embedded tissues. The expressions of the target genes were also examined in osteosarcoma samples using immunohistochemistry. Overexpression of miR-194 inhibited tumor growth and metastasis of osteosarcoma probably by downregulating CDH2 and IGF1R. miR-194 may prove to be a promising therapeutic agent for osteosarcoma.
引用
收藏
页码:1437 / 1449
页数:13
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