MicroRNA-506 Up-Regulation Inhibits Growth and Invasion in Non-Small Cell Lung Cancer Cells by Possibly Targeting Sphingosine Kinase 1

Increasing evidence has confirmed that dysregulation of microRNAs (miRNAs) contributes to the proliferation and invasion of human cancers. Previous studied have shown that dysregulation of miR-506 is in numerous cancers. However, the roles of miR-506 in human non-small cell lung cancer (NSCLC) have not been well clarified. Therefore, this study was to investigate the biological functions and molecular mechanisms of miR-506 in NSCLC cell lines, discussing whether it could be a therapeutic biomarker of NSCLC in the future. In our study, we found that miR-506 was down-regulated in NSCLC cell lines and tissues. Moreover, the low level of miR-506 was associated with increased expression of Sphingosine kinase 1 (SPHK1) in NSCLC cells. Up-regulation of miR-506 significantly inhibited cell proliferation, invasion, MMP-2 and -9 expressions of NSCLC cells. Bioinformatics analysis predicted that the SPHK1 was a potential target of miR-506. Further study by luciferase reporter assay demonstrated that miR-506 could directly target SPHK1. Overexpression of SPHK1 in NSCLC cells transfected with miR-506 mimic partially reversed the inhibitory of miR-506. In conclusion, nniR-506 inhibited cell proliferation and invasion in NSCLC cells by downregulation of SPHK1, and that downregulation of SPHK1 was essential for the miR-506-inhibited cell invasion and in NSCLC cells.