Skip to main content

Advertisement

SpringerLink
Log in

From small to big: microRNAs as new players in medulloblastomas

  • Review
  • Published:
Tumor Biology

Abstract

Medulloblastomas (MB) are the most common malignant neoplasms of the central nervous system in children. Although the molecular basis of medulloblastoma has received considerable attention over the past decade, the underlying cellular and molecular mechanisms of medulloblastoma initiation, maintenance, and progression remain unclear. MicroRNAs (miRNAs) are short non-coding RNAs that function as key regulators of diverse biological processes by exerting negative gene regulation at the post-transcriptional level. Emerging evidence indicates that miRNAs play an important role in the development of human cancers; miRNA deregulation results in altered activities of downstream tumor suppressors, oncogenes, and other signaling molecules. In this review, we comprehensively discuss the versatile roles of miRNAs in medulloblastoma and their potential applications in the diagnosis, prognosis, and treatment of this malignancy. As a rapidly evolving field of basic and biomedical sciences, miRNA research will certainly have a revolutionary impact on the management of medulloblastoma.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Rossi A, Caracciolo V, Russo G, Reiss K, Giordano A. Medulloblastoma: from molecular pathology to therapy. Clin Cancer Res. 2008;14:971–6.

    Article  PubMed  CAS  Google Scholar 

  2. MacDonald TJ. Aggressive infantile embryonal tumors. J Child Neurol. 2008;23:1195–204.

    Article  PubMed  Google Scholar 

  3. Packer RJ. Childhood brain tumors: accomplishments and ongoing challenges. J Child Neurol. 2008;23:1122–7.

    Article  PubMed  Google Scholar 

  4. Bhat SR, Goodwin TL, Burwinkle TM, Lansdale MF, Dahl GV, Huhn SL, et al. Profile of daily life in children with brain tumors: an assessment of health-related quality of life. J Clin Oncol. 2005;23:5493–500.

    Article  PubMed  Google Scholar 

  5. Srivastava VK, Nalbantoglu J. The cellular and developmental biology of medulloblastoma: current perspectives on experimental therapeutics. Cancer Biol Ther. 2010;9:843–52.

    Article  PubMed  CAS  Google Scholar 

  6. Kim W, Choy W, Dye J, Nagasawa D, Safaee M, Fong B, et al. The tumor biology and molecular characteristics of medulloblastoma identifying prognostic factors associated with survival outcomes and prognosis. J Clin Neurosci. 2011;18:886–90.

    Article  PubMed  CAS  Google Scholar 

  7. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.

    Article  PubMed  CAS  Google Scholar 

  8. He L, Hannon GJ. MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet. 2004;5:522–31.

    Article  PubMed  CAS  Google Scholar 

  9. Cho WC. MicroRNAs in cancer—from research to therapy. Biochim Biophys Acta. 2010;1805:209–17.

    PubMed  CAS  Google Scholar 

  10. Esquela-Kerscher A, Slack FJ. Oncomirs—microRNAs with a role in cancer. Nat Rev Cancer. 2006;6:259–69.

    Article  PubMed  CAS  Google Scholar 

  11. Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer. 2006;6:857–66.

    Article  PubMed  CAS  Google Scholar 

  12. Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993;75:843–54.

    Article  PubMed  CAS  Google Scholar 

  13. Kozomara A, Griffiths-Jones S. miRBase: integrating microRNA annotation and deep-sequencing data. Nucleic Acids Res. 2011;39:D152–7.

    Article  PubMed  Google Scholar 

  14. Lee Y, Jeon K, Lee JT, Kim S, Kim VN. MicroRNA maturation: stepwise processing and subcellular localization. EMBO J. 2002;21:4663–70.

    Article  PubMed  CAS  Google Scholar 

  15. Zeng Y, Yi R, Cullen BR. MicroRNAs and small interfering RNAs can inhibit mRNA expression by similar mechanisms. Proc Natl Acad Sci U S A. 2003;100:9779–84.

    Article  PubMed  CAS  Google Scholar 

  16. Zamore PD, Tuschl T, Sharp PA, Bartel DP. RNAi: double-stranded RNA directs the ATP-dependent cleavage of mRNA at 21 to 23 nucleotide intervals. Cell. 2000;101:25–33.

    Article  PubMed  CAS  Google Scholar 

  17. Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 2005;120:15–20.

    Article  PubMed  CAS  Google Scholar 

  18. Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E, et al. Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A. 2002;99:15524–9.

    Article  PubMed  CAS  Google Scholar 

  19. Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, et al. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci U S A. 2004;101:2999–3004.

    Article  PubMed  CAS  Google Scholar 

  20. Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, et al. MicroRNA expression profiles classify human cancers. Nature. 2005;435:834–8.

    Article  PubMed  CAS  Google Scholar 

  21. Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, et al. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci U S A. 2006;103:2257–61.

    Article  PubMed  CAS  Google Scholar 

  22. Yanaihara N, Caplen N, Bowman E, Seike M, Kumamoto K, Yi M, et al. Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell. 2006;9:189–98.

    Article  PubMed  CAS  Google Scholar 

  23. Pichler M, Winter E, Stotz M, Eberhard K, Samonigg H, Lax S, et al. Down-regulation of KRAS-interacting miRNA-143 predicts poor prognosis but not response to EGFR-targeted agents in colorectal cancer. Br J Cancer. 2012;106:1826–32.

    Article  PubMed  CAS  Google Scholar 

  24. Zhi F, Chen X, Wang S, Xia X, Shi Y, Guan W, et al. The use of hsa-miR-21, hsa-miR-181b and hsa-miR-106a as prognostic indicators of astrocytoma. Eur J Cancer. 2010;46:1640–9.

    Article  PubMed  CAS  Google Scholar 

  25. Giovannetti E, Funel N, Peters GJ, Del Chiaro M, Erozenci LA, Vasile E, et al. MicroRNA-21 in pancreatic cancer: correlation with clinical outcome and pharmacologic aspects underlying its role in the modulation of gemcitabine activity. Cancer Res. 2010;70:4528–38.

    Article  PubMed  CAS  Google Scholar 

  26. Ferretti E, De Smaele E, Miele E, Laneve P, Po A, Pelloni M, et al. Concerted microRNA control of Hedgehog signalling in cerebellar neuronal progenitor and tumour cells. EMBO J. 2008;27:2616–27.

    Article  PubMed  CAS  Google Scholar 

  27. Ferretti E, De Smaele E, Po A, Di Marcotullio L, Tosi E, Espinola MS, et al. MicroRNA profiling in human medulloblastoma. Int J Cancer. 2009;124:568–77.

    Article  PubMed  CAS  Google Scholar 

  28. Northcott PA, Fernandez LA, Hagan JP, Ellison DW, Grajkowska W, Gillespie Y, et al. The miR-17/92 polycistron is up-regulated in sonic hedgehog-driven medulloblastomas and induced by N-myc in sonic hedgehog-treated cerebellar neural precursors. Cancer Res. 2009;69:3249–55.

    Article  PubMed  CAS  Google Scholar 

  29. Uziel T, Karginov FV, Xie S, Parker JS, Wang YD, Gajjar A, et al. The miR-17 92 cluster collaborates with the Sonic Hedgehog pathway in medulloblastoma. Proc Natl Acad Sci U S A. 2009;106:2812–7.

    Article  PubMed  CAS  Google Scholar 

  30. Lu Y, Ryan SL, Elliott DJ, Bignell GR, Futreal PA, Ellison DW, et al. Amplification and overexpression of Hsa-miR-30b, Hsa-miR-30d and KHDRBS3 at 8q24.22-q24.23 in medulloblastoma. PLoS One. 2009;4:e6159.

    Article  PubMed  Google Scholar 

  31. Bai AH, Milde T, Remke M, Rolli CG, Hielscher T, Cho YJ, et al. MicroRNA-182 promotes leptomeningeal spread of non-sonic hedgehog-medulloblastoma. Acta Neuropathol. 2012;123:529–38.

    Article  PubMed  CAS  Google Scholar 

  32. Gokhale A, Kunder R, Goel A, Sarin R, Moiyadi A, Shenoy A, et al. Distinctive microRNA signature of medulloblastomas associated with the WNT signaling pathway. J Cancer Res Ther. 2010;6:521–9.

    Article  PubMed  CAS  Google Scholar 

  33. Venkataraman S, Alimova I, Fan R, Harris P, Foreman N, Vibhakar R. MicroRNA 128a increases intracellular ROS level by targeting Bmi-1 and inhibits medulloblastoma cancer cell growth by promoting senescence. PLoS One. 2010;5:e10748.

    Article  PubMed  Google Scholar 

  34. He L, Thomson JM, Hemann MT, Hernando-Monge E, Mu D, Goodson S, et al. A microRNA polycistron as a potential human oncogene. Nature. 2005;435:828–33.

    Article  PubMed  CAS  Google Scholar 

  35. Pan X, Wang ZX, Wang R. MicroRNA-21: a novel therapeutic target in human cancer. Cancer Biol Ther. 2011;10:1224–32.

    PubMed  Google Scholar 

  36. Grunder E, D’Ambrosio R, Fiaschetti G, Abela L, Arcaro A, Zuzak T, et al. MicroRNA-21 suppression impedes medulloblastoma cell migration. Eur J Cancer. 2011;47:2479–90.

    Article  PubMed  CAS  Google Scholar 

  37. Weeraratne SD, Amani V, Neiss A, Teider N, Scott DK, Pomeroy SL, et al. miR-34a confers chemosensitivity through modulation of MAGE-A and p53 in medulloblastoma. Neuro Oncol. 2011;13:165–75.

    Article  PubMed  CAS  Google Scholar 

  38. de Antonellis P, Medaglia C, Cusanelli E, Andolfo I, Liguori L, De Vita G, et al. MiR-34a targeting of Notch ligand delta-like 1 impairs CD15+/CD133+ tumor-propagating cells and supports neural differentiation in medulloblastoma. PLoS One. 2011;6:e24584.

    Article  PubMed  Google Scholar 

  39. Pierson J, Hostager B, Fan R, Vibhakar R. Regulation of cyclin dependent kinase 6 by microRNA 124 in medulloblastoma. J Neurooncol. 2008;90:1–7.

    Article  PubMed  CAS  Google Scholar 

  40. Li KK, Pang JC, Ching AK, Wong CK, Kong X, Wang Y, et al. miR-124 is frequently down-regulated in medulloblastoma and is a negative regulator of SLC16A1. Hum Pathol. 2009;40:1234–43.

    Article  PubMed  CAS  Google Scholar 

  41. Weeraratne SD, Amani V, Teider N, Pierre-Francois J, Winter D, Kye MJ, et al. Pleiotropic effects of miR-183 96 182 converge to regulate cell survival, proliferation and migration in medulloblastoma. Acta Neuropathol. 2012;123:539–52.

    Article  PubMed  CAS  Google Scholar 

  42. Garzia L, Andolfo I, Cusanelli E, Marino N, Petrosino G, De Martino D, et al. MicroRNA-199b-5p impairs cancer stem cells through negative regulation of HES1 in medulloblastoma. PLoS One. 2009;4:e4998.

    Article  PubMed  Google Scholar 

  43. Fouladi M, Gajjar A, Boyett JM, Walter AW, Thompson SJ, Merchant TE, et al. Comparison of CSF cytology and spinal magnetic resonance imaging in the detection of leptomeningeal disease in pediatric medulloblastoma or primitive neuroectodermal tumor. J Clin Oncol. 1999;17:3234–7.

    PubMed  CAS  Google Scholar 

  44. Cho YJ, Tsherniak A, Tamayo P, Santagata S, Ligon A, Greulich H, et al. Integrative genomic analysis of medulloblastoma identifies a molecular subgroup that drives poor clinical outcome. J Clin Oncol. 2011;29:1424–30.

    Article  PubMed  Google Scholar 

  45. Eberhart CG, Kratz J, Wang Y, Summers K, Stearns D, Cohen K, et al. Histopathological and molecular prognostic markers in medulloblastoma: c-myc, N-myc, TrkC, and anaplasia. J Neuropathol Exp Neurol. 2004;63:441–9.

    PubMed  CAS  Google Scholar 

  46. Lv SQ, Kim YH, Giulio F, Shalaby T, Nobusawa S, Yang H, et al. Genetic alterations in microRNAs in medulloblastomas. Brain Pathol. 2012;22:230–9.

    Article  PubMed  CAS  Google Scholar 

  47. Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, et al. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 2008;18:997–1006.

    Article  PubMed  CAS  Google Scholar 

  48. Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A. 2008;105:10513–8.

    Article  PubMed  CAS  Google Scholar 

  49. Park NJ, Zhou H, Elashoff D, Henson BS, Kastratovic DA, Abemayor E, et al. Salivary microRNA: discovery, characterization, and clinical utility for oral cancer detection. Clin Cancer Res. 2009;15:5473–7.

    Article  PubMed  CAS  Google Scholar 

  50. Hanke M, Hoefig K, Merz H, Feller AC, Kausch I, Jocham D, et al. A robust methodology to study urine microRNA as tumor marker: microRNA-126 and microRNA-182 are related to urinary bladder cancer. Urol Oncol. 2010;28:655–61.

    Article  PubMed  CAS  Google Scholar 

  51. Chen X, Gao C, Li H, Huang L, Sun Q, Dong Y, et al. Identification and characterization of microRNAs in raw milk during different periods of lactation, commercial fluid, and powdered milk products. Cell Res. 2010;20:1128–37.

    Article  PubMed  CAS  Google Scholar 

Download references

Conflicts of interest

None

Author information

Authors and Affiliations

  1. Modern Medical Research Center, Third Affiliated Hospital of Soochow University, 185#, Juqian Road, Changzhou, 213003, Jiangsu, China

    Feng Zhi, Suinuan Wang, Rong Wang & Yilin Yang

  2. Department of Neurosurgery, Third Affiliated Hospital of Soochow University, 185#, Juqian Road, Changzhou, 213003, Jiangsu, China

    Feng Zhi & Xiwei Xia

Authors
  1. Feng Zhi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Suinuan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rong Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiwei Xia
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yilin Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Xiwei Xia or Yilin Yang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhi, F., Wang, S., Wang, R. et al. From small to big: microRNAs as new players in medulloblastomas. Tumor Biol. 34, 9–15 (2013). https://doi.org/10.1007/s13277-012-0579-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-012-0579-9

Keywords

Search

Navigation