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MicroRNA-125b Promotes Tumor Metastasis Through Targeting Tumor Protein 53-induced Nuclear Protein 1 in Patients with Non-small-cell Lung Cancer

Overview
Journal Cancer Cell Int
Publisher Biomed Central
Date 2015 Sep 22
PMID 26388699
Citations 22
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Abstract

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.

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