MiR‐128 up‐regulation inhibits Reelin and DCX expression and reduces neuroblastoma cell motility and invasiveness

Abstract

MicroRNAs are a class of sophisticated regulators of gene expression, acting as post‐transcriptional inhibitors that recognize their target mRNAs through base pairing with short regions along the 3'UTRs. Several microRNAs are tissue specific, suggesting a specialized role in tissue differentiation or maintenance, and quite a few are critically involved in tumorigenesis. We studied miR‐128, a brain‐enriched microRNA, in retinoic acid‐differentiated neuroblastoma cells, and we found that this microRNA is up‐regulated in treated cells, where it down‐modulates the expression of two proteins involved in the migratory potential of neural cells: Reelin and DCX. Consistently, miR‐128 ectopic overexpression suppressed Reelin and DCX, whereas the LNA antisensemediated miR‐128 knockdown caused the two proteins to increase. Ectopic miR‐128 overexpression reduced neuroblastoma cell motility and invasiveness, and impaired cell growth. Finally, the analysis of a small series of primary human neuroblastomas showed an association between high levels of miR‐128 expression and favorable features, such as favorable Shimada category or very young age at diagnosis. Thus, we provide evidence for a role for miR‐128 in the molecular events modulating neuroblastoma progression and aggressiveness.—Evangelisti, C., Florian, M. C., Massimi, I., Dominici, C., Giannini, G., Galardi, S., Buè, M. C., Massalini, S., McDowell, H. P., Messi, E., Gulino, A., Farace, M. G., Ciafrè, S. A. MiR‐128 up‐regulation inhibits Reelin and DCX expression and reduces neuroblastoma cell motility and invasiveness. FASEBJ. 23, 4276‐4287 (2009). www.fasebj.org