Global expression of microRNAs in neurospheres in primary cultures of glioblastoma treated with temozolomide and ionizing radiation.
Authors: de Assis Cirino Mucio Luiz , Rodrigues Andressa Romualdo , Sabedot Thais Sarraf , Neto Fermino Sanches Lizarte , Pugliesi Renata , Peria Fernanda Maris , Bisson Gabriela Silva , Noushmehr Houtan , Tiezzi Daniel Guimarães , Junior Carlos Gilberto Carlotti , da Cunha Tirapelli Daniela Pretti 
Published: June 2021

Introduction

Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor in adults, characterized by aggressive growth, limited response to therapy and inexorable recurrence. Due to the extremely unfavorable prognosis of GBM, it is important to develop more effective diagnostic and therapeutic strategies. The discovery of a subpopulation of cells in the tumor called cancer stem cells (CSCs) opens a wide field in understanding the aggressiveness of GBM. In addition to self‐renewal and tumorigenesis, these cells are known for their resistance to radiotherapy and chemotherapy compared to other cancer cells. In this context, many studies have evaluated the role of microRNAs associated with various molecular mechanisms and the development and proliferation of various types of diseases, including cancer. Studies have shown that in brain tumors these miRNAs have altered levels of expression. In addition, they are essential in the regulation of tumor stem cells.

Objectives

To evaluate the expression of microRNAs in neurospheres and attached cells established after cell culture of samples from ten patients diagnosed with GBM submitted to treatments with temozolomide and ionizing radiation, isolated or associated.

Materials and Methods

Initially, cell cultures were established from the GBMs samples and then these were treated with temozolomide and ionizing radiation. The cell viability evaluation was made with trypan blue 48 hours after treatments and the quantification of microRNA expression was made by Taqman Low Density Array (TLDA®). A description of clinical and epidemiological data was also carried out on 10 patients, who provided tumor samples for this study, followed by immunohistochemical evaluation of the expression of IDH1‐mutated in these samples.

Results

After treatment with temozolomide and ionizing radiation, we found some statistically significant differences between the cell viability of neurospheres and attached cells. Regarding the expression of the microRNAs, five were differentially expressed between neurospheres and attached cells. miRNAs‐101, ‐124a and ‐1275 showed increased expression in neurospheres treated with ionizing radiation. miR‐155 showed increased expression in attached cells treated with ionizing radiation. miR‐138 showed increased expression in attached cells treated with temozolomide. The median overall survival of the series of cases was 56.5 years. There was expression of IDH1‐mutated in 90% of cases, and death in 40%.

Conclusion

After treatments with temozolomide and ionizing radiation, no statistically significant differences were observed between the cell viability of neurospheres and attached cells. Regarding the overall expression of miRNAs, these presented a differential expression pattern in the cell groups, and may be modulated by the proposed treatments.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.