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

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