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MiRNA expression profiling in human gliomas: upregulated miR-363 increases cell survival and proliferation

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Tumor Biology

Abstract

The role of microRNAs (miRNAs) in glioma biology is increasingly recognized. To investigate the regulatory mechanisms governing the malignant signature of gliomas with different grades of malignancy, we analyzed miRNA expression profiles in human grade I–IV tumor samples and primary glioma cell cultures. Multiplex real-time PCR was used to profile miRNA expression in a set of World Health Organization (WHO) grade I (pilocytic astrocytoma), II (diffuse fibrillary astrocytoma), and IV (glioblastoma multiforme) astrocytic tumors and primary glioma cell cultures. Primary glioma cell cultures were used to evaluate the effect of transfection of specific miRNAs and miRNA inhibitors. miRNA microarray showed that a set of miRNAs was consistently upregulated in all glioma samples. miR-363 was upregulated in all tumor specimens and cell lines, and its expression correlated with tumor grading. The transfection of glioma cells with the specific inhibitor of miR-363 increased the expression level of tumor suppressor growth-associated protein 43 (GAP-43). Transfection of miR-363 induced cell survival, while inhibition of miR-363 significantly reduced glioma cell viability. Furthermore, miRNA-363 inhibition induced the downregulation of AKT, cyclin-D1, matrix metalloproteinase (MMP)-2, MMP-9, and Bcl-2 and upregulation of caspase 3. Together, these data suggest that the upregulation of miR-363 may play a role in malignant glioma signature.

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Authors and Affiliations

  1. Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy

    Alfredo Conti, Sara G. Romeo, Annamaria Cama, Domenico La Torre, Salvatore Cardali, Filippo F. Angileri & Antonino Germanò

  2. Department of Adulthood and Childhood Pathology “G. Barresi”, University of Messina, Messina, Italy

    Valeria Barresi, Gaetana Pezzino, Chiara Tomasello & Guido Ferlazzo

  3. Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy

    Francesca Polito, Rosamaria Di Giorgio & M’hammed Aguennouz

Authors
  1. Alfredo Conti
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  2. Sara G. Romeo
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  3. Annamaria Cama
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  4. Domenico La Torre
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  5. Valeria Barresi
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  6. Gaetana Pezzino
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  7. Chiara Tomasello
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  8. Salvatore Cardali
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  9. Filippo F. Angileri
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  10. Francesca Polito
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  11. Guido Ferlazzo
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  12. Rosamaria Di Giorgio
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  13. Antonino Germanò
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  14. M’hammed Aguennouz
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Corresponding author

Correspondence to Alfredo Conti.

Ethics declarations

This study was approved by the local Institutional Reveiw Board (IRB) (Comitato Etico Interaziendale della Provincia di Messina, http://polime.it/comitato_etico_interaziendale); Prot.: E09/14 approved on February 12th 2014

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Alfredo Conti and Sara G. Romeo equally contributed to this study.

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Conti, A., Romeo, S.G., Cama, A. et al. MiRNA expression profiling in human gliomas: upregulated miR-363 increases cell survival and proliferation. Tumor Biol. 37, 14035–14048 (2016). https://doi.org/10.1007/s13277-016-5273-x

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  • DOI: https://doi.org/10.1007/s13277-016-5273-x

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