Global expression profile of microRNAs in neurospheres and adherent cells of primary cultures of glioblastoma treated with ionizing radiation and temozolomide

Abstract

Glioblastomas (GBM) are the most common primary tumors malignant in the brain, and show high mortality rate. Despite the current advances in therapy, the GBMs are extremely resistant to ionizing radiation and chemotherapy, and the number of relapse is high. Studies bring this eminent tumorigenic potential due to the presence of a subpopulation of neoplastic cells with characteristics of stem cells, called tumor stem cells (CSCs). In gliomas, the isolation of tumor stem cells have been done by antigenic markers and observing the culture conditions of normal neural stem cells in vitro. That is, the floating proliferation of tumor cells when cultured, are analogous to neurospheres derived from normal neural stem cells in defined culture conditions. It is believed that CSCs are responsible for the restoration of the tumor and the low efficiency of the treatment, as these cells demonstrate malignant properties as tumorigenesis, chemoresistance and radioresistance. The practical implication of this finding is that no current therapy is able to suppress or stop the proliferation of these cells. Several microRNAs have been linked to the development and proliferation of glioblastomas, associated with different molecular mechanisms. Studies have shown that these microRNAs in brain tumors exhibit altered expression levels, one of the essential mechanisms for the regulation of tumor stem cells (CSCs). Objectives: Analyze the global expression of microRNAs in neurospheres and adherent cells from primary cultures of patients with glioblastoma subjected to treatment with ionizing radiation and temozolomide, combined or isolated. Material and Methods: Primary cultures of 10 patients diagnosed with glioblastoma will be used and the global analysis of expression will be performed by technique TaqMan ® Low Density Array microRNA (TLDA) to quantify the expression of microRNAs in both groups (neurospheres and cells acquired) in each of the treatment subgroups: control, ionizing radiation , temozolomide and temozolomide associated with ionizing radiation. (AU)