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



D. Qian, Department of Pediatric Surgery, The Affiliated Hospital of Medical College Qingdao University, Qingdao 266003, China

Fax: +86 532 82911999

Tel: +86 532 82911885

E-mail: dongqianqingdao2012@yahoo.cn

W. Renjie, Department of Clinical Laboratory, The Affiliated Hospital of Logistics College of Chinese People's Armed Police Force, Tianjin 300162, China

Fax: +86 22 60578615

Tel: +86 22 60578616

E-mail: wangrenjie2012@yahoo.cn


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.