Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
July-2017 Volume 38 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
July-2017 Volume 38 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

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
  • View Affiliations / Copyright

    Affiliations: Department of Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA, Department of Biological Sciences, Fordham University, Bronx, NY 10458, USA
  • Pages: 545-550
    |
    Published online on: May 24, 2017
       https://doi.org/10.3892/or.2017.5664
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



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.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Park JR, Bagatell R, London WB, Maris JM, Cohn SL, Mattay KK and Hogarty M: COG Neuroblastoma Committee: Children's Oncology Group's 2013 blueprint for research: Neuroblastoma. Pediatr Blood Cancer. 60:985–993. 2013. View Article : Google Scholar : PubMed/NCBI

2 

Bell E, Chen L, Liu T, Marshall GM, Lunec J and Tweddle DA: MYCN oncoprotein targets and their therapeutic potential. Cancer Lett. 293:144–157. 2010. View Article : Google Scholar : PubMed/NCBI

3 

Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI

4 

Schulte JH, Schowe B, Mestdagh P, Kaderali L, Kalaghatgi P, Schlierf S, Vermeulen J, Brockmeyer B, Pajtler K, Thor T, et al: Accurate prediction of neuroblastoma outcome based on miRNA expression profiles. Int J Cancer. 127:2374–2385. 2010. View Article : Google Scholar : PubMed/NCBI

5 

Fontana L, Fiori ME, Albini S, Cifaldi L, Giovinazzi S, Forloni M, Boldrini R, Donfrancesco A, Federici V, Giacomini P, et al: Antagomir-17-5p abolishes the growth of therapy-resistant neuroblastoma through p21 and BIM. PLoS One. 3:e22362008. View Article : Google Scholar : PubMed/NCBI

6 

Hu H, Du L, Nagabayashi G, Seeger RC and Gatti RA: ATM is down-regulated by N-Myc-regulated microRNA-421. Proc Natl Acad Sci USA. 107:1506–1511. 2010. View Article : Google Scholar : PubMed/NCBI

7 

Buckley PG, Alcock L, Bryan K, Bray I, Schulte JH, Schramm A, Eggert A, Mestdagh P, De Preter K, Vandesompele J, et al: Chromosomal and microRNA expression patterns reveal biologically distinct subgroups of 11q- neuroblastoma. Clin Cancer Res. 16:2971–2978. 2010. View Article : Google Scholar : PubMed/NCBI

8 

Chen Y and Stallings RL: Differential patterns of microRNA expression in neuroblastoma are correlated with prognosis, differentiation, and apoptosis. Cancer Res. 67:976–983. 2007. View Article : Google Scholar : PubMed/NCBI

9 

Shohet JM, Ghosh R, Coarfa C, Ludwig A, Benham AL, Chen Z, Patterson DM, Barbieri E, Mestdagh P, Sikorski DN, et al: A genome-wide search for promoters that respond to increased MYCN reveals both new oncogenic and tumor suppressor microRNAs associated with aggressive neuroblastoma. Cancer Res. 71:3841–3851. 2011. View Article : Google Scholar : PubMed/NCBI

10 

Ma L, Young J, Prabhala H, Pan E, Mestdagh P, Muth D, Teruya-Feldstein J, Reinhardt F, Onder TT, Valastyan S, et al: miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis. Nat Cell Biol. 12:247–256. 2010.PubMed/NCBI

11 

Wei JS, Song YK, Durinck S, Chen QR, Cheuk AT, Tsang P, Zhang Q, Thiele CJ, Slack A, Shohet J, et al: The MYCN oncogene is a direct target of miR-34a. Oncogene. 27:5204–5213. 2008. View Article : Google Scholar : PubMed/NCBI

12 

Lovén J, Zinin N, Wahlström T, Müller I, Brodin P, Fredlund E, Ribacke U, Pivarcsi A, Påhlman S and Henriksson M: MYCN-regulated microRNAs repress estrogen receptor-α (ESR1) expression and neuronal differentiation in human neuroblastoma. Proc Natl Acad Sci USA. 107:1553–1558. 2010. View Article : Google Scholar : PubMed/NCBI

13 

Haug BH, Henriksen JR, Buechner J, Geerts D, Tømte E, Kogner P, Martinsson T, Flægstad T, Sveinbjørnsson B and Einvik C: MYCN-regulated miRNA-92 inhibits secretion of the tumor suppressor DICKKOPF-3DKK3) in neuroblastoma. Carcinogenesis. 32:1005–1012. 2011. View Article : Google Scholar : PubMed/NCBI

14 

Buechner J, Tømte E, Haug BH, Henriksen JR, Løkke C, Flægstad T and Einvik C: Tumour-suppressor microRNAs let-7mir-101 target the proto-oncogene MYCN and inhibit cell proliferation in MYCN-amplified neuroblastoma. Br J Cancer. 105:296–303. 2011. View Article : Google Scholar : PubMed/NCBI

15 

Bray I, Bryan K, Prenter S, Buckley PG, Foley NH, Murphy DM, Alcock L, Mestdagh P, Vandesompele J, Speleman F, et al: Widespread dysregulation of MiRNAs by MYCN amplification and chromosomal imbalances in neuroblastoma: Association of miRNA expression with survival. PLoS One. 4:e78502009. View Article : Google Scholar : PubMed/NCBI

16 

Schulte JH, Horn S, Otto T, Samans B, Heukamp LC, Eilers UC, Krause M, Astrahantseff K, Klein-Hitpass L, Buettner R, et al: MYCN regulates oncogenic MicroRNAs in neuroblastoma. Int J Cancer. 122:699–704. 2008. View Article : Google Scholar : PubMed/NCBI

17 

Olive V, Jiang I and He L: mir-17-92, a cluster of miRNAs in the midst of the cancer network. Int J Biochem Cell Biol. 42:1348–1354. 2010. View Article : Google Scholar : PubMed/NCBI

18 

Chagnovich D, Fayos BE and Cohn SL: Differential activity of ELAV-like RNA-binding proteins in human neuroblastoma. J Biol Chem. 271:33587–33591. 1996. View Article : Google Scholar : PubMed/NCBI

19 

Lazarova DL, Spengler BA, Biedler JL and Ross RA: HuD, a neuronal-specific RNA-binding protein, is a putative regulator of N-myc pre-mRNA processing/stability in malignant human neuroblasts. Oncogene. 18:2703–2710. 1999. View Article : Google Scholar : PubMed/NCBI

20 

Grandinetti KB, Spengler BA, Biedler JL and Ross RA: Loss of one HuD allele on chromosome #1p selects for amplification of the N-myc proto-oncogene in human neuroblastoma cells. Oncogene. 25:706–712. 2006. View Article : Google Scholar : PubMed/NCBI

21 

Walton JD, Kattan DR, Thomas SK, Spengler BA, Guo HF, Biedler JL, Cheung NK and Ross RA: Characteristics of stem cells from human neuroblastoma cell lines and in tumors. Neoplasia. 6:838–845. 2004. View Article : Google Scholar : PubMed/NCBI

22 

Schulte JH, Marschall T, Martin M, Rosenstiel P, Mestdagh P, Schlierf S, Thor T, Vandesompele J, Eggert A, Schreiber S, et al: Deep sequencing reveals differential expression of microRNAs in favorable versus unfavorable neuroblastoma. Nucleic Acids Res. 38:5919–5928. 2010. View Article : Google Scholar : PubMed/NCBI

23 

O'Donnell KA, Wentzel EA, Zeller KI, Dang CV and Mendell JT: c-Myc-regulated microRNAs modulate E2F1 expression. Nature. 435:839–843. 2005. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
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
Copy and paste a formatted citation
x
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
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team