Advertisement

Child's Nervous System

, Volume 26, Issue 3, pp 279–283 | Cite as

Upregulation of mir-221 and mir-222 in atypical teratoid/rhabdoid tumors: potential therapeutic targets

  • Simone Treiger Sredni
  • Maria de Fátima Bonaldo
  • Fabrício Falconi Costa
  • Chiang-Ching Huang
  • Christopher Allan Hamm
  • Veena Rajaram
  • Tadanori Tomita
  • Stewart Goldman
  • Jared Marshall Bischof
  • Marcelo Bento Soares
Brief Communication

Abstract

Purpose

The aim of this study is to search for new therapeutic targets for atypical teratoid–rhabdoid tumors (ATRT).

Methods

To achieve this, we compared the expression of 365 microRNAs among ATRT, medulloblastomas, and normal brain.

Results

MiR-221 and miR-222 were within the top differentially expressed microRNAs. The deregulated expression of miR221/222 was demonstrated to inhibit the expression of the tumor suppressor and inhibitor of cell cycle p27Kip1. Here, we demonstrated the negative regulation of p27Kip1 by miR-221/222 in ATRT using microarray, real-time reverse transcriptase polymerase chain reaction, and immunohistochemistry.

Conclusion

As anti-miR therapy was recently proposed as an alternative treatment for cancer, these findings suggest that anti-miR-221/222 therapy might have therapeutic potential in ATRT.

Keywords

Atypical teratoid/rhabdoid tumors miR221 miR222 p27Kip1 

Notes

Acknowledgments

This project was supported by the Dr. Ralph and Marian C. Falk Medical Research Trust, the Rally Foundation for Childhood Cancer Research, and the Maeve McNicholas Memorial Foundation.

Ethical standards

This study has been approved by the Children’s Memorial Hospital Institutional Review Board (IRB#2009-13778) and had therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki. All persons gave their informed consent prior to their inclusion in the study.

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Strother D (2005) Atypical teratoid rhabdoid tumors of childhood: diagnosis, treatment and challenges. Expert Rev Anticancer Ther 5:907–915CrossRefPubMedGoogle Scholar
  2. 2.
    Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297CrossRefPubMedGoogle Scholar
  3. 3.
    Wurdinger T, Costa FF (2007) Molecular therapy in the microRNA era. Pharmacogenomics J 7:297–304CrossRefPubMedGoogle Scholar
  4. 4.
    Oyharcabal-Bourden V, Kalifa C, Gentet JC, Frappaz D, Edan C, Chastagner P, Sariban E, Pagnier A, Babin A, Pichon F, Neuenschwander S, Vinchon M, Bours D, Mosseri V, Le Gales C, Ruchoux M, Carrie C, Doz F (2005) Standard-risk medulloblastoma treated by adjuvant chemotherapy followed by reduced-dose craniospinal radiation therapy: a French Society of Pediatric Oncology Study. J Clin Oncol 23:4726–4734CrossRefPubMedGoogle Scholar
  5. 5.
    Chen C, Ridzon DA, Broomer AJ, Zhou Z, Lee DH, Nguyen JT, Barbisin M, Xu NL, Mahuvakar VR, Andersen MR, Lao KQ, Livak KJ, Guegler KJ (2005) Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res 33(20):e179CrossRefPubMedGoogle Scholar
  6. 6.
    Pfaffl MW (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29(9):e45CrossRefPubMedGoogle Scholar
  7. 7.
    Judkins AR, Mauger J, Ht A, Roke LB, Biegel JA (2004) Immunohistochemical analysis of hSNF5/INI1 in pediatric CNS neoplasms. Am J Surg Pathol 28:644–650PubMedGoogle Scholar
  8. 8.
    Ishizaki Y (2006) Control of proliferation and differentiation of neural precursor cells: focusing on the developing cerebellum. J Pharmacol Sci 101:183–188CrossRefPubMedGoogle Scholar
  9. 9.
    Chi SN, Zimmerman MA, Yao X, Cohen KJ, Burger P, Biegel JA, Rorke-Adams LB, Fisher MJ, Janss A, Mazewski C, Goldman S, Manley PE, Bowers DC, Bendel A, Rubin J, Turner CD, Marcus KJ, Goumnerova L, Ullrich NJ, Kieran MW (2009) Intensive multimodality treatment for children with newly diagnosed CNS atypical teratoid rhabdoid tumor. J Clin Oncol 27:385–389CrossRefPubMedGoogle Scholar
  10. 10.
    Koff A (2006) How to decrease p27Kip1 levels during tumor development. Cancer Cell 9:75–76CrossRefPubMedGoogle Scholar
  11. 11.
    le Sage C, Nagel R, Egan DA, Schrier M, Mesman E, Mangiola A, Anile C, Maira G, Mercatelli N, Ciafrè SA, Farace MG, Agami R (2007) Regulation of the p27(Kip1) tumor suppressor by miR-221 and miR-222 promotes cancer cell proliferation. EMBO J 26:3699–3708CrossRefPubMedGoogle Scholar
  12. 12.
    Zhang C, Kang C, You Y, Pu P, Yang W, Zhao P, Wang G, Zhang A, Jia Z, Han L, Jiang H (2009) Co-suppression of miR-221/222 cluster suppresses human glioma cell growth by targeting p27kip1 in vitro and in vivo. Int J Oncol 34:1653–1660CrossRefPubMedGoogle Scholar
  13. 13.
    Ciafre SA, Galardi S, Mangiola A, Ferracin M, Liu CG, Sabatino G, Negrini M, Maira G, Croce CM, Farace MG (2005) Extensive modulation of a set of microRNAs in primary glioblastoma. Biochem Biophys Res Commun 334:1351–1358CrossRefPubMedGoogle Scholar
  14. 14.
    Gillies JK, Lorimer IA (2007) Regulation of p27Kip1 by miRNA 221/222 in glioblastoma. Cell Cycle 6:2005–2009PubMedGoogle Scholar
  15. 15.
    Schiappacassi M, Lovat F, Canzonieri V, Belletti B, Berton S, Di Stefano D, Vecchione A, Colombatti A, Baldassarre G (2008) p27Kip1 expression inhibits glioblastoma growth, invasion, and tumor-induced neoangiogenesis. Mol Cancer Ther 7:1164–1175CrossRefPubMedGoogle Scholar
  16. 16.
    Fornari F, Gramantieri L, Ferracin M, Veronese A, Sabbioni S, Calin GA, Grazi GL, Giovannini C, Croce CM, Bolondi L, Negrini M (2008) MiR-221 controls CDKN1C/p57 and CDKN1B/p27 expression in human hepatocellular carcinoma. Oncogene 27:5651–5661CrossRefPubMedGoogle Scholar
  17. 17.
    Visone R, Russo L, Pallante P, De Martino I, Ferraro A, Leone V, Borbone E, Petrocca F, Alder H, Croce CM, Fusco A (2007) MicroRNAs (miR)-221 and miR-222, both overexpressed in human thyroid papillary carcinomas, regulate p27Kip1 protein levels and cell cycle. Endocr Relat Cancer 14:791–798CrossRefPubMedGoogle Scholar
  18. 18.
    Galardi S, Mercatelli N, Giorda E, Massalini S, Frajese GV, Ciafré SA, Farrace MG (2007) miR-221 and miR-222 expression affects the proliferation potential of human prostate carcinoma cell lines by targeting p27Kip1. J Biol Chem 282:23716–23724CrossRefPubMedGoogle Scholar
  19. 19.
    Mercatelli N, Coppola V, Bonci D, Miele F, Costantini A, Guadagnoli M, Bonanno E, Muto G, Frajese GV, De Maria R, Spagnoli LG, Farace MG, Ciafrè SA (2008) The inhibition of the highly expressed miR-221 and miR-222 impairs the growth of prostate carcinoma xenografts in mice. PLoS ONE 3(12):e4029CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Simone Treiger Sredni
    • 1
  • Maria de Fátima Bonaldo
    • 1
  • Fabrício Falconi Costa
    • 1
  • Chiang-Ching Huang
    • 2
  • Christopher Allan Hamm
    • 1
    • 3
  • Veena Rajaram
    • 4
  • Tadanori Tomita
    • 5
  • Stewart Goldman
    • 6
  • Jared Marshall Bischof
    • 1
  • Marcelo Bento Soares
    • 1
  1. 1.Cancer Biology and Epigenomics Program, Children’s Memorial Research Center, Department of Pediatrics, Feinberg School of Medicine, Children’s Memorial Hospital ChicagoUSA
  2. 2.Department of Preventive Medicine, Feinberg School of MedicineNorthwestern UniversityChicagoUSA
  3. 3.Interdisciplinary Graduate Program in GeneticsUniversity of IowaIowa CityUSA
  4. 4.Division of Anatomic PathologyChildren’s Memorial HospitalChicagoUSA
  5. 5.Division of Pediatric NeurosurgeryChildren’s Memorial HospitalChicagoUSA
  6. 6.Division of Hematology/Oncology/TransplantationChildren’s Memorial HospitalChicagoUSA

Personalised recommendations