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

FEBS J. 2013 Feb;280(3):855-66. doi: 10.1111/febs.12074. Epub 2013 Jan 16.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Movement / genetics
  • GPI-Linked Proteins / genetics*
  • GPI-Linked Proteins / metabolism
  • Gene Expression Regulation, Neoplastic
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Matrix Metalloproteinase 9 / genetics*
  • Matrix Metalloproteinase 9 / metabolism
  • MicroRNAs / genetics*
  • Models, Genetic
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Neuroblastoma / genetics*
  • Neuroblastoma / metabolism
  • Neuroblastoma / pathology
  • RNA Interference
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spectrometry, Fluorescence

Substances

  • 3' Untranslated Regions
  • GPI-Linked Proteins
  • MIRN15 microRNA, human
  • MicroRNAs
  • RECK protein, human
  • Green Fluorescent Proteins
  • Matrix Metalloproteinase 9