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Reciprocal antagonistic regulation of N-myc mRNA by miR‑17 and the neuronal-specific RNA-binding protein HuD

  • Authors:
    • Leleesha Samaraweera
    • Barbara A. Spengler
    • Robert A. Ross

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  • Published online on: May 24, 2017     https://doi.org/10.3892/or.2017.5664
  • Pages: 545-550
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Abstract

Neuroblastoma is a childhood cancer originating from embryonic neural crest cells. Amplification of the proto‑oncogene N-myc, seen in ~30% of neuroblastoma tumors, is a marker for poor prognosis. Recently discovered small regulatory RNAs, microRNAs (miRNAs), are implicated in cancers, including neuroblastoma. miRNAs downregulate the expression of genes by binding to the 3'-untranslated regions (3'-UTRs), thereby inhibiting translation or inducing degradation of cognate mRNAs. Our study sought to identify miRNAs that regulate N-myc expression and thereby malignancy in neuroblastoma. miRNAs whose expression negatively correlates with N-myc expression were identified from a miRNA microarray of 4 N-myc-amplified neuroblastoma cell lines. Three of these miRNAs (miR-17, miR-20a and miR-18a) belong to the miR-17-92 cluster, previously shown to be upregulated by N-myc. qPCR validation of these miRNAs in a larger panel of cell lines revealed that levels of miR-17 were inversely proportional to N-myc mRNA amounts in the N-myc-amplified cell lines. Notably, miR-17 also downregulated N-myc protein synthesis in the N-myc-amplified cells, thereby generating a negative feedback regulatory loop between the proto-oncogene and this miRNA. Moreover, the neuronal-specific RNA-binding protein HuD (ELAVL4), which regulates the processing/stability of N-myc mRNA, competes with miR-17 for a binding site in the 3'-UTR of N-myc. Thus, N-myc levels appear to be modulated by the antagonistic interactions of both miR-17, as a negative regulator, and HuD, as a positive regulator, providing further evidence of the complex cellular control mechanisms of this oncogene in N-myc-amplified neuroblastoma cells.
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July-2017
Volume 38 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Samaraweera L, Spengler BA and Ross RA: Reciprocal antagonistic regulation of N-myc mRNA by miR‑17 and the neuronal-specific RNA-binding protein HuD. Oncol Rep 38: 545-550, 2017.
APA
Samaraweera, L., Spengler, B.A., & Ross, R.A. (2017). Reciprocal antagonistic regulation of N-myc mRNA by miR‑17 and the neuronal-specific RNA-binding protein HuD. Oncology Reports, 38, 545-550. https://doi.org/10.3892/or.2017.5664
MLA
Samaraweera, L., Spengler, B. A., Ross, R. A."Reciprocal antagonistic regulation of N-myc mRNA by miR‑17 and the neuronal-specific RNA-binding protein HuD". Oncology Reports 38.1 (2017): 545-550.
Chicago
Samaraweera, L., Spengler, B. A., Ross, R. A."Reciprocal antagonistic regulation of N-myc mRNA by miR‑17 and the neuronal-specific RNA-binding protein HuD". Oncology Reports 38, no. 1 (2017): 545-550. https://doi.org/10.3892/or.2017.5664