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 antisense-mediated 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., Massimi, I., Dominici, C., Giannini, G., Galardi, S., et al. (2009). MiR-128 up-regulation inhibits Reelin and DCX expression and reduces neuroblastoma cell motility and invasiveness. THE FASEB JOURNAL, 23(12), 4276-4287 [10.1096/fj.09-134965].

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

GALARDI, SILVIA;BUE', MARIA CRISTINA;FARACE, MARIA GIULIA;CIAFRE', SILVIA ANNA
2009-12-01

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 antisense-mediated 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.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/13
English
Con Impact Factor ISI
Base Sequence; Neuropeptides; Neuroblastoma; Extracellular Matrix Proteins; Humans; Cell Adhesion Molecules, Neuronal; Cell Line, Tumor; Microtubule-Associated Proteins; Neurons; Neoplasm Invasiveness; Serine Endopeptidases; Gene Expression Regulation; Nerve Tissue Proteins; MicroRNAs; Molecular Sequence Data; Cell Movement; Tretinoin
Evangelisti, C., Florian, M., Massimi, I., Dominici, C., Giannini, G., Galardi, S., et al. (2009). MiR-128 up-regulation inhibits Reelin and DCX expression and reduces neuroblastoma cell motility and invasiveness. THE FASEB JOURNAL, 23(12), 4276-4287 [10.1096/fj.09-134965].
Evangelisti, C; Florian, M; Massimi, I; Dominici, C; Giannini, G; Galardi, S; Bue', Mc; Massalini, S; Mcdowell, H; Messi, E; Gulino, A; Farace, Mg; Ciafre', Sa
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/9150
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