MicroRNA-128a, BMI1 polycomb ring finger oncogene, and reactive oxygen species inhibit the growth of U-87 MG glioblastoma cells following exposure to X-ray radiation

Abstract

Radiotherapy is an important therapeutic strategy for the treatment of numerous types of malignant tumors, including glioma. However, radioresistance and anti-apoptotic mechanisms decrease the efficacy of radiotherapy in many patients with glioma. BMI1 polycomb ring finger oncogene (Bmi-1) is an oncogene associated with radioresistance in tumor cells. MicroRNA (miRNA).128a is a brain-specific miRNA, which suppresses Bmi-1 expression. The present study investigated the effects of various radiation intensities on U.87 MG glioma cells, as well as the role of reactive oxygen species (ROS), Bmi-1, and miRNA-128a in the cellular response to radiotherapy. The response of U.87 MG cells following exposure to X-ray radiation was assessed using a cell growth curve and inhibition ratio. Cell cycle distribution and the levels of intracellular ROS were evaluated by flow cytometry. The mRNA expression levels of Bmi-1 and those of miRNA-128a in U-87 MG cells exposed to X-ray radiation were evaluated by reverse transcription.quantitative polymerase chain reaction. X-ray radiation did not decrease the number of U.87 MG cells; however, it did inhibit cellular growth in a dose.dependent manner. Following exposure to X-ray radiation for 24.h, cell cycle distribution was altered, with an increase in the number of cells in G0/G1-phase. The mRNA expression levels of Bmi-1 were downregulated in the 1.and 2-Gy groups, and upregulated in the 6.and 8.Gy groups. The expression levels of miRNA-128a were upregulated in the 1.and 2.Gy groups, and downregulated in the 8-Gy group. The levels of ROS were increased following exposure to-2-Gy, and treatment with N-acetyl cysteine was able to induce radioresistance. These results suggested that U-87 MG cells exhibited radioresistance. High doses of X-ray radiation increased the expression levels of Bmi-1, which may be associated with the evasion of cellular senescence. miRNA-128a and its downstream target gene Bmi-1 may have an important role in the radioresistance of U-87 MG glioma cells. In addition, ROS may be involved in the mechanisms underlying the inhibitory effects of X-ray radiation in U-87 MG cells, and the downregulation of ROS may induce radioresistance.