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    Reduced EGFR and increased miR-221 is associated with increased resistance to temozolomide and radiotherapy in glioblastoma

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    Author
    Areeb, Z; Stuart, SF; West, AJ; Gomez, J; Nguyen, HPT; Paradiso, L; Zulkifli, A; Jones, J; Kaye, AH; Morokoff, AP; ...
    Date
    2020-10-20
    Source Title
    Scientific Reports
    Publisher
    NATURE RESEARCH
    University of Melbourne Author/s
    Morokoff, Andrew; Kaye, Andrew; Luwor, Rodney; Nguyen, Hong; Paradiso, Lucia; Zulkifli, Ahmad Azri; Jones, Jordan
    Affiliation
    Surgery (RMH)
    Microbiology and Immunology
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    Areeb, Z., Stuart, S. F., West, A. J., Gomez, J., Nguyen, H. P. T., Paradiso, L., Zulkifli, A., Jones, J., Kaye, A. H., Morokoff, A. P. & Luwor, R. B. (2020). Reduced EGFR and increased miR-221 is associated with increased resistance to temozolomide and radiotherapy in glioblastoma. SCIENTIFIC REPORTS, 10 (1), https://doi.org/10.1038/s41598-020-74746-x.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/251718
    DOI
    10.1038/s41598-020-74746-x
    Open Access at PMC
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576591
    Abstract
    Despite aggressive treatment with temozolomide and radiotherapy and extensive research into alternative therapies there has been little improvement in Glioblastoma patient survival. Median survival time remains between 12 and 15 months mainly due to treatment resistance and tumor recurrence. In this study, we aimed to explore the underlying mechanisms behind treatment resistance and the lack of success with anti-EGFR therapy in the clinic. After generating a number of treatment resistant Glioblastoma cell lines we observed that resistant cell lines lacked EGFR activation and expression. Furthermore, cell viability assays showed resistant cells were significantly less sensitive to the anti-EGFR agents when compared to parental cell lines. To further characterise the resistance mechanism in our cells microRNA prediction software identified miR-221 as a negative regulator of EGFR expression. miR-221 was up-regulated in our resistant cell lines, and this up-regulation led to a significant reduction in EGFR expression in both our cultured cell lines and a large cohort of glioblastoma patient tumor tissue.

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