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MiR-192 directly binds and regulates Dicer1 expression in neuroblastoma.

Feinberg-Gorenshtein G, Guedj A, Shichrur K, Jeison M, Luria D, Kodman Y, Ash S, Feinmesser M, Edry L, Shomron N, Weizman A, Yaniv I, Avigad S - PLoS ONE (2013)

Bottom Line: We were able to show through a dual luciferase assay and side-directed mutational analysis that miR-192 directly binds the 3' UTR of Dicer1 on positions 1232-1238 and 2282-2288.An increase in cell viability, proliferation and migration rates were evident in NB cells transfected with miR-192-mimic.Yet, there was a significant decrease in proliferation when NB cells were transfected with an miR-192-inhibitor We suggest that miR-192 might be a key player in NB by regulating Dicer1 expression.

View Article: PubMed Central - PubMed

Affiliation: Molecular Oncology, Felsenstein Medical Research Center, Petah Tikva, Israel ; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

ABSTRACT
Neuroblastoma (NB) arises from the embryonic neural crest and is the most common extracranial solid tumor in children under 5 years of age. Reduced expression of Dicer1 has recently been shown to be in correlation with poor prognosis in NB patients. This study aimed to investigate the mechanisms that could lead to the down-regulation of Dicer1 in neuroblastoma. We used computational prediction to identify potential miRs down-regulating Dicer1 in neuroblastoma. One of the miRs that were predicted to target Dicer1 was miR-192. We measured the levels of miR-192 in 43 primary tumors using real time PCR. Following the silencing of miR-192, the levels of dicer1 cell viability, cell proliferation and migration capability were analyzed. Multivariate analysis identified miR-192 as an independent prognostic marker for relapse in neuroblastoma patients (p=0.04). We were able to show through a dual luciferase assay and side-directed mutational analysis that miR-192 directly binds the 3' UTR of Dicer1 on positions 1232-1238 and 2282-2288. An increase in cell viability, proliferation and migration rates were evident in NB cells transfected with miR-192-mimic. Yet, there was a significant decrease in proliferation when NB cells were transfected with an miR-192-inhibitor We suggest that miR-192 might be a key player in NB by regulating Dicer1 expression.

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Related in: MedlinePlus

Kaplan Meier analysis by Dicer1 expression.Kaplan Meier analysis for PFS by Dicer1 expression (n=47): high and low expression levels of Dicer1 were determined as above (n=24) or below (n=23) the median expression level.
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pone-0078713-g002: Kaplan Meier analysis by Dicer1 expression.Kaplan Meier analysis for PFS by Dicer1 expression (n=47): high and low expression levels of Dicer1 were determined as above (n=24) or below (n=23) the median expression level.

Mentions: Expression levels of Dicer1 mRNA were analyzed in a cohort of 47 NB samples. We identified a significant correlation between PFS and Dicer1 expression at 10 years: patients with high Dicer1 expression levels had 87% PFS versus 59% in patients with low Dicer1 expression (p=0.032, Figure 2). No significant correlation was identified between Dicer1 expression levels and clinical parameters.


MiR-192 directly binds and regulates Dicer1 expression in neuroblastoma.

Feinberg-Gorenshtein G, Guedj A, Shichrur K, Jeison M, Luria D, Kodman Y, Ash S, Feinmesser M, Edry L, Shomron N, Weizman A, Yaniv I, Avigad S - PLoS ONE (2013)

Kaplan Meier analysis by Dicer1 expression.Kaplan Meier analysis for PFS by Dicer1 expression (n=47): high and low expression levels of Dicer1 were determined as above (n=24) or below (n=23) the median expression level.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3815303&req=5

pone-0078713-g002: Kaplan Meier analysis by Dicer1 expression.Kaplan Meier analysis for PFS by Dicer1 expression (n=47): high and low expression levels of Dicer1 were determined as above (n=24) or below (n=23) the median expression level.
Mentions: Expression levels of Dicer1 mRNA were analyzed in a cohort of 47 NB samples. We identified a significant correlation between PFS and Dicer1 expression at 10 years: patients with high Dicer1 expression levels had 87% PFS versus 59% in patients with low Dicer1 expression (p=0.032, Figure 2). No significant correlation was identified between Dicer1 expression levels and clinical parameters.

Bottom Line: We were able to show through a dual luciferase assay and side-directed mutational analysis that miR-192 directly binds the 3' UTR of Dicer1 on positions 1232-1238 and 2282-2288.An increase in cell viability, proliferation and migration rates were evident in NB cells transfected with miR-192-mimic.Yet, there was a significant decrease in proliferation when NB cells were transfected with an miR-192-inhibitor We suggest that miR-192 might be a key player in NB by regulating Dicer1 expression.

View Article: PubMed Central - PubMed

Affiliation: Molecular Oncology, Felsenstein Medical Research Center, Petah Tikva, Israel ; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

ABSTRACT
Neuroblastoma (NB) arises from the embryonic neural crest and is the most common extracranial solid tumor in children under 5 years of age. Reduced expression of Dicer1 has recently been shown to be in correlation with poor prognosis in NB patients. This study aimed to investigate the mechanisms that could lead to the down-regulation of Dicer1 in neuroblastoma. We used computational prediction to identify potential miRs down-regulating Dicer1 in neuroblastoma. One of the miRs that were predicted to target Dicer1 was miR-192. We measured the levels of miR-192 in 43 primary tumors using real time PCR. Following the silencing of miR-192, the levels of dicer1 cell viability, cell proliferation and migration capability were analyzed. Multivariate analysis identified miR-192 as an independent prognostic marker for relapse in neuroblastoma patients (p=0.04). We were able to show through a dual luciferase assay and side-directed mutational analysis that miR-192 directly binds the 3' UTR of Dicer1 on positions 1232-1238 and 2282-2288. An increase in cell viability, proliferation and migration rates were evident in NB cells transfected with miR-192-mimic. Yet, there was a significant decrease in proliferation when NB cells were transfected with an miR-192-inhibitor We suggest that miR-192 might be a key player in NB by regulating Dicer1 expression.

Show MeSH
Related in: MedlinePlus