TY - JOUR
T1 - MiR-128 up-regulation inhibits Reelin and DCX expression and reduces neuroblastoma cell motility and invasiveness
AU - Evangelisti, Cristina
AU - Florian, Maria Carolina
AU - Massimi, Isabella
AU - Dominici, Carlo
AU - Giannini, Giuseppe
AU - Galardi, Silvia
AU - Buè, Maria Cristina
AU - Massalini, Simone
AU - McDowell, Heather P.
AU - Messi, Elio
AU - Gulino, Alberto
AU - Farace, Maria Giulia
AU - Ciafrè, Silvia Anna
PY - 2009/12
Y1 - 2009/12
N2 - 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.
AB - 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.
KW - MicroRNA
KW - Neuronal
KW - Retinoic acid
KW - Tumor
UR - http://www.scopus.com/inward/record.url?scp=72749114951&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=72749114951&partnerID=8YFLogxK
U2 - 10.1096/fj.09-134965
DO - 10.1096/fj.09-134965
M3 - Article
C2 - 19713529
AN - SCOPUS:72749114951
VL - 23
SP - 4276
EP - 4287
JO - FASEB Journal
JF - FASEB Journal
SN - 0892-6638
IS - 12
ER -