Abstract

BackgroundMicroRNAs (miRNAs or miRs) can participate in the development and progression of neuroblastoma. Many studies have indicated that miR-429 can participate in tumor development. However, the mechanism underlying miR-429-mediated progression of neuroblastoma remains largely unclear.MethodsColony formation and apoptosis assays were used to determine the effect of miR-429 on cell proliferation. Its impact on cell migration was determined using the wound-healing and Transwell assays. The target gene of miR-429 was confirmed via western blotting and luciferase reporter assays. A nude mouse xenograft model with miR-429 overexpression was used to assess the effect on tumor growth.ResultsOur findings indicate that miR-429 is downregulated in neuroblastoma cell lines. We also found that it can induce apoptosis and inhibit proliferation in cells of those lines. MiR-429 can bind to the 3′-UTR of IKKβ mRNA and overexpression of IKKβ can reverse cell proliferation, blocking the effect of miR-429. Furthermore, miR-429 overexpression inhibited neuroblastoma growth in our nude mouse xenograft model.ConclusionWe provide important insight into miR-429 as a tumor suppressor through interaction with IKKβ, which is a catalytic subunit of the IKK complex that activates NF-κB nuclear transport. Our results demonstrate that miR-429 may be a new target for the treatment of neuroblastoma.

Highlights

  • Neuroblastoma, which is a malignancy with high mortality, originates from neural crest pluripotent cells [1,2,3]

  • Results miR-429 was underexpressed in neuroblastoma cells We first compared miR-429 expression in neuroblastoma cell lines and human neuronal cells

  • Our results showed that miR-429 expression was significantly lower in neuroblastoma cell lines than in normal cells (Fig. 1a)

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Summary

Introduction

Neuroblastoma, which is a malignancy with high mortality, originates from neural crest pluripotent cells [1,2,3]. It has a high incidence in children under the age of 15 [4]. Great progress has been made in clinical treatment, the survival rate of patients with metastatic neuroblastoma has not been improved [6]. Clarifying the mechanisms underlying neuroblastoma progression is necessary for development of more effective treatments. MicroRNAs (miRNAs or miRs) can participate in the development and progression of neuroblastoma. The mechanism underlying miR-429mediated progression of neuroblastoma remains largely unclear

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