MicroRNA-15a promotes neuroblastoma migration by targeting reversion-inducing cysteine-rich protein with Kazal motifs (RECK) and regulating matrix metalloproteinase-9 expression

Abstract

In this study, we found that the expression of miR-15a was positively correlated with neuroblastoma (NB) clinical pathological stage and was negatively correlated with reversion-inducing cysteine-rich protein with Kazal motifs (RECK) expression. Using the enhanced green fluorescent protein (EGFP) reporter construct carrying the 3′-UTR of RECK, we identified RECK as a direct target of miR-15a. Suppression of miR-15a significantly decreased the migration ability of GI-LA-N and SK-N-SH cell lines, whereas overexpression of miR-15a increased the migration ability; these effects could be partly reversed by RECK inhibition or ectopic expression. Moreover, inhibition of miR-15a significantly increased secreted matrix metalloproteinase-9 expression in culture medium through regulating the expression of RECK. These findings provide new insights into the characteristics of the miR-15a-RECK-matrix metalloproteinase-9 axis in NB progression, especially in NB migration and invasion. In our study, we demonstrated (a) miR-15a was positively correlated with NB clinical pathological stages; (b) miR-15a directly targets RECK 3′UTR and regulates its expression; (c) miRNA-15a regulated NB cell migrations through targeting RECK; (d) miR-15a regulates secreted MMP-9 expression through targeting RECK and (e) an axis of miR-15a/RECK/MMP-9 plays an important role in regulating NB migration and invasion. © 2012 The Authors Journal compilation.