Expression of microRNAs associated with apoptosis in neurospheres of glioblastoma cell line subjected to treatment with ionizing radiation and temozolomide.

Introduction Glioblastomas (GBM) are the most common malignant primary tumors in the brain, and show high mortality rate. Despite the current advances in the 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 cancer 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, among them programmed cell death. 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 To evaluate the effect of ionizing radiation and temozolomide, alone or associated, on the expression of miRNAs that act as tumor suppressors (miR‐15 and miR‐16) and as oncogene (miR‐21), and adhered cells in neurospheres in culture of glioblastoma cell line (U343‐MG). Materials and Methods The trypan blue was used to examine cell viability before and after treatment, and method of real time PCR to check the expression of microRNAs in time 0h, considered to be immediately after the treatments, and 48h after exposure to treatments. Results and Conclusions The presented microRNAs are differentially expressed when comparing the different treatment modalities and time. We also observed differences between adhered cells and neurospheres. The oncogene miR‐21 remained with higher expression on treatment with ionizing radiation in neurospheres compared with the group of adherent cells. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .