Abstract
BackgroundNeuroblastoma is a neural crest-derived tumor and is the most common cancer in children less than 1 year of age. We hypothesized that aberrations in genes that control the cell cycle could play an important role in the pathogenesis of neuroblastoma and could provide a tractable therapeutic target.MethodsIn this study, we screened 131 genes involved in cell cycle regulation at different levels by analyzing the effect of siRNA-mediated gene silencing on the proliferation of neuroblastoma cells.ResultsMarked reductions in neuroblastoma cellular proliferation were recorded after knockdown of CCND1 or PLK1. We next showed that pharmacological inhibition of cyclin D1 dependent kinases 4/6 (CDK4/6) with PD 0332991 (palbociclib) reduced the growth of neuroblastoma cell lines, induced G1 cell cycle arrest, and inhibited the cyclin D1-Rb pathway.ConclusionSelective inhibition of CDK4/6 using palbociclib may provide a new therapeutic option for treating neuroblastoma.Electronic supplementary materialThe online version of this article (doi:10.1186/s12935-015-0224-y) contains supplementary material, which is available to authorized users.
Highlights
Neuroblastoma is a neural crest-derived tumor and is the most common cancer in children less than 1 year of age
Our results showed that knockdown of CCND1 induces a reduction in cellular proliferation in the majority of the neuroblastoma cell lines in comparison to the scrambled siRNA negative control (Fig. 2)
We show that palbociclib induces a G1 cell cycle arrest in neuroblastoma cells, which is in line with previous reports in other cancer types [10]
Summary
Neuroblastoma is a neural crest-derived tumor and is the most common cancer in children less than 1 year of age. Neuroblastoma is a solid childhood tumor that arises from the sympathoadrenal lineage of the neural crest during development [1] It represents the most common cancer in children younger than 1 year [2] and is a heterogeneous disease that may either have a very good prognosis (e.g., stage 4S neuroblastoma) or a dismal outlook (e.g., MYCN-amplified neuroblastoma) [1]. The siRNA library was used to assess the effect of knockdown of cell cycle regulators on the proliferation of neuroblastoma cells. This approach is expected to result in the identification of genes that are required for proliferation or survival of neuroblastoma cells, and may serve as new therapeutic targets.
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