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miR-221/222 overexpession in human glioblastoma increases invasiveness by targeting the protein phosphate PTPμ

Oncogene volume 31, pages 858–868 (2012)Cite this article

Abstract

Glioblastoma is the most frequent brain tumor in adults and is the most lethal form of human cancer. Despite the improvements in treatments, survival of patients remains poor. In order to identify microRNAs (miRs) involved in glioma tumorigenesis, we evaluated, by a miRarray, differential expression of miRs in the tumorigenic glioma LN-18, LN-229 and U87MG cells compared with the non-tumorigenic T98G cells. Among different miRs we focused our attention on miR-221 and -222. We demonstrated the presence of a binding site for these two miRs in the 3′ untranslated region of the protein tyrosine phosphatase μ (PTPμ). Previous studies indicated that PTPμ suppresses cell migration and is downregulated in glioblastoma. Significantly, we found that miR-221 and -222 overexpression induced a downregulation of PTPμ as analyzed by both western blot and real-time PCR. Furthermore, miR-222 and -221 induced an increase in cell migration and growth in soft agar in glioma cells. Interestingly, the re-expression of PTPμ gene was able to revert the miR-222 and -221 effects on cell migration. Furthermore, we found an inverse correlation between miR-221 and -222 and PTPμ in human glioma cancer samples. In conclusion, our results suggest that miR-221 and -222 regulate glioma tumorigenesis at least in part through the control of PTPμ protein expression.

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Acknowledgements

This work was partially supported by funds from Associazione Italiana Ricerca sul Cancro, AIRC to GC (Grant n.ro 10620) and MERIT (RBNE08E8CZ_002) to GC. CQ is supported by a Federazione Italiana Ricerca sul Cancro (FIRC) Post-Doctoral Research Fellowship. CZ is supported by an American-Italian Cancer Foundation Post-Doctoral Research Fellowship.

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Authors and Affiliations

  1. Department of Cellular and Molecular Biology and Pathology, ‘Federico II’ University of Naples, Naples, Italy

    C Quintavalle, C Zanca, M Iaboni & G Condorelli

  2. Department of Molecular Virology, Immunology and Medical Genetics, Human Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA

    M Garofalo, G Nuovo & C M Croce

  3. Fondazione IRCCS SDN, Naples, Italy

    G Romano & M Incoronato

  4. Dipartimento di Scienze Biomorfologiche e Funzionali, Sezione di Anatomia Patologica e Fitopatologia,

    M del Basso De Caro

  5. Instituto Oftalmico/Hospital Universitario Gregorio Marañon, Madrid, Spain

    J C Martinez-Montero

  6. IEOS, CNR, Naples, Italy

    G Condorelli

  7. Facoltà di Scienze Biotecnologiche, ‘Federico II’ University of Naples, Naples, Italy

    G Condorelli

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  1. C Quintavalle
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  2. M Garofalo
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  9. G Nuovo
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  10. C M Croce
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Correspondence to G Condorelli.

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Quintavalle, C., Garofalo, M., Zanca, C. et al. miR-221/222 overexpession in human glioblastoma increases invasiveness by targeting the protein phosphate PTPμ. Oncogene 31, 858–868 (2012). https://doi.org/10.1038/onc.2011.280

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