MicroRNA-125b promotes tumor metastasis through targeting tumor protein 53-induced nuclear protein 1 in patients with non-small-cell lung cancer

Cancer Cell International

Tao Ren³  Jingang Zhang²  Yuanyuan Wang³  Shan Shan³  Chunhong Wang³  Yang Han⁴  Qinchuan Li¹ 

[1] Department of Cardiothoracic Surgery, East Hospital, Tongji University School of Medicine, Shanghai, China;Service Center for Family planning, Maternal and Child Health Care, Lanshan, Linyi, Shandong, China;Department of Respiratory Medicine, East Hospital, Tongji University School of Medicine, 150 Jimo Road, Pudong New Area, Shanghai, 200120, China;Department of Pathology, East Hospital, Tongji University School of Medicine, Shanghai, China

关键词: TP53INP1;    miR-125b;    Metastasis;    NSCLC;   

Others  :  1233620
DOI  :  10.1186/s12935-015-0233-x

 received in 2015-02-26, accepted in 2015-08-24,  发布年份 2015

【 摘 要 】

Background

Lung cancer, predominantly non-small-cell lung cancer (NSCLC), is the leading cause of cancer deaths worldwide. There is a great need to identify critical effectors involved in metastasis of NSCLC that will facilitate the development of new therapeutic strategies. Here we evaluated the potential role of miR-125b in the metastasis of NSCLC cells.

Methods

Human NSCLC cells were isolated from surgical tissues with Cancer Cell Isolation Kit. Expressions of miR-125b and TP53INP1 were detected with real-time PCR and western blot. Human miR-125b mimics, miR-125b inhibitor, TP53INP1 expression plasmid and TP53INP1 siRNA were transfected into NSCLC cells with nucleofector transfection kit. NSCLC metastasis was determined with adhesion assay, invasive assay and lung tumor metastasis model.

Results

The expression of miR-125b was significantly higher in poorly differentiated NSCLC cells that are endowed with high metastatic potentials. Up-regulation of miR-125b could enhance the metastatic potential of NSCLC cells in vitro and in vivo, while down-regulation of miR-125b resulted in decreased metastatic potentials in vitro and in vivo. Further, tumor protein 53-induced nuclear protein 1 (TP53INP1) was an important target of miR-125b involved in metastasis of NSCLC cells. TP53INP1 served as a negative regulator of NSCLC metastasis. Decreased expression of TP53INP1 in tumor tissues was inversely associated with their expression of miR-125b, significantly lower in poorly differentiated tumors and inversely correlated with the clinical stages in patients with NSCLC.

Conclusions

These findings demonstrated that miR-125b promoted tumor metastasis via targeting TP53INP1 in human NSCLC cells, which uncovered a real clinical relevance of microRNAs in tumor biology, and provided novel potential candidates for NSCLC clinical practice.

【 授权许可】

   
2015 Li et al.

【 图 表 】

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