Abstract
Neuroblastoma is a common tumor of the peripheral nervous system in children. Highly aggressive MYC-drivenneuroblastoma is defined by increased MYC and/or MYCN expression. HDAC8 overexpression is associated with advanced neuroblastoma. Previously, we have demonstrated that transient knockdown of both Myc and Hdac8 using siRNA significantly suppressed neuroblastoma cells proliferation compared to knockdown of either target in vitro. In this study, we further investigated whether combinational targeting Myc and Hdac8 in neuroblastoma xenograft mice model is consistent with our previous findings. Intratumoral treatment with siRNA-MYC and siRNA-HDAC8 reduced the levels of the target MYC protein by 64% and HDAC8 by 85%; in addition, we found that the average tumor growth was reduced by 80% compared to that of control tumors treated with NC-siRNA. Our results suggest the potential therapeutic effect of the combination of siRNA-MYC and siRNA-HDAC8 for neuroblastoma treatment.
Highlights
Neuroblastoma is the most frequently diagnosed extracranial solid tumor in children
We explored the therapeutic effect of treatment with the combination of small inhibitory RNA (siRNA)-HDAC8 + siRNA-MYC on neuroblastoma tumor xenografts in mice
One group of mice treated with a 3 nmol negative control siRNA (NCsiRNA) and other group of mice were treated with a 3 nmol combination of siRNA-HDAC8 + siRNA-MYC. siRNAs was inoculated into tumors by intratumoral injections every third day
Summary
Neuroblastoma is the most frequently diagnosed extracranial solid tumor in children. About 90% of cases occur in children less than 5 years old and it is rare in adults. Of cancer deaths in children, about 15% are due to neuroblastoma [1]. MYC is an oncogenic transcription factor that is overexpressed in many types of cancer. MYC has been shown to directly upregulate a protumorigenic group of miRNAs and represses several suppressor miRNAs, contributing to tumorigenesis [3]. MYC overexpression can upregulate the oncogenic miR-17-92 cluster, that are directly activated in lymphoma [4], and can repress several suppressor miRNAs [3]. The MYC gene is amplified in various human cancers, including in lung carcinoma, breast carcinoma, and colon carcinoma [5]
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