RETRACTED: Overexpression of miR-499-5p inhibits non-small cell lung cancer proliferation and metastasis by targeting VAV3 (Retracted Article)

被引:72
作者
Li, Ming [1 ]
Zhang, Shenjun [2 ]
Wu, Ning [3 ]
Wu, Liang [4 ]
Wang, Changhui [1 ]
Lin, Yinping [1 ,2 ]
机构
[1] Tongji Univ, Shanghai Peoples Hosp 10, Dept Resp Med, Shanghai 200072, Peoples R China
[2] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Biol, Shanghai 200031, Peoples R China
[3] Fudan Univ, Huashan Hosp, Dept Thorac Surg, Shanghai 200032, Peoples R China
[4] Tongji Univ, Shanghai Pulm Hosp, Dept Thorac Surg, Shanghai 200433, Peoples R China
基金
中国国家自然科学基金;
关键词
MICRORNAS; RECEPTOR; PROGRESSION;
D O I
10.1038/srep23100
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Dysregulation of miRNAs is reported to be involved in the invasion and metastasis of lung cancer. Previous studies showed that low serum miR-499 expression was associated with advanced TNM stage and poor prognosis. The present study is carried out to evaluate the biological functions of miR-499-5p in lung cancer. We demonstrated that miR-499-5p was significantly reduced in NSCLC tissues and correlated with poor clinical outcomes. Overexpression of miR-499-5p inhibited cell proliferation and induced apoptosis in vitro and in vivo. Furthermore, miR-499-5p overexpression also inhibited NSCLC metastasis in vitro and in vivo. Using bioinformatics tools, we identified VAV3 as a candidate target of miR-499-5p, and demonstrated that restoration of miR-499-5p expression in NSCLC cells downregulated VAV3 expression while inhibition of miR-499-5p upregulated VAV3 expression. Luciferase reporter assays showed that miR-499-5p targeted 3'-UTR of VAV3. Moreover, cancer growth, proliferation and metastasis were decreased and apoptosis was increased after VAV3 blockage induced by miR-499-5p overexpression. We conclude that miR-499-5p functions as a tumor suppressor by targeting VAV3. This finding may provide a therapeutic approach for future treatment of NSCLC.
引用
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页数:10
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