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Potential of Anti-Cancer Therapy Based on Anti-miR-155 Oligonucleotides in Glioma and Brain Tumours

Authors

  • Palmiro Poltronieri,

    Corresponding author
    1. National Research Council, CNR-ISPA, via Monteroni, 73100 Lecce, Italy
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  • Pietro I. D’Urso,

    1. Department of Neurological and Psychiatric Sciences, Section of Neurosurgery, University of Bari Medical School, p.zza G. Cesare 11, 70124 Bari, Italy
    2. Neurosurgery Department, King’s College Hospital, Denmark Hill, London SE5 9RS, UK
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  • Valeria Mezzolla,

    1. Department of Biological and Environmental Science and Technology, University of Salento, via Monteroni, 73100 , Italy
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  • Oscar F. D’Urso

    1. Department of Biological and Environmental Science and Technology, University of Salento, via Monteroni, 73100 , Italy
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Corresponding author: Palmiro Poltronieri, palmiro.poltronieri@ispa.cnr.it

Abstract

MicroRNAs are aberrantly expressed in many cancers and can exert tumour-suppressive or oncogenic functions. As oncomirs promote growth of cancer cells and support survival during chemotherapy, thus microRNA-silencing therapies could be a valuable approach to be associated with anticancer drugs and chemotherapy treatments. miR-155 microRNA was found overexpressed in different types of cancer, such as leukaemias (PML, B-cell lymphomas), lung cancer and glioblastoma. GABA-A receptor downregulation was found correlated with glioma grading, with decreasing levels associated with higher grade of malignancies. A relationship between knock-down of miR-155 and re-expression of GABRA 1 protein in vivo was recently individuated. This finding has implication on the effectiveness of RNA-silencing approaches against miR-155 with the scope to control proliferation and signalling pathways regulated by GABA-A receptor. Applying microRNAs for treatment of brain tumours poses several problems, and fields to be solved are mainly the passage of the brain–blood barrier and the targeted delivery to specific cell types. Glioblastoma multiforme cells bud off microvesicles that deliver cytoplasmic contents to nearby cells. Thus, the exploitation of these mechanisms to deliver antagomir therapeutics targeting microvescicles in the brain could take the lead in the near future in the treatment for brain cancers in substitution of invasive surgical intervention.

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