Bmi-1 induces radioresistance by suppressing senescence in human U87 glioma cells

Abstract

Radiotherapy is the main locoregional control modality for a number of types of malignant tumors, including glioblastoma. However, radiotherapy fails to prevent recurrence in numerous patients due to the intrinsic radioresistance of cancer cells. Cell senescence is significant in tumor suppressor mechanisms and is closely associated with the radioresistance of cancer cells. Bmi-1 has been proposed to be an oncogene that can induce anti-senescence in tumor cells. The present study investigated the response of U87 glioma cells to radiation exposure and the role of Bmi-1 in the response following radiotherapy. Cell apoptosis and cell cycle distribution were assessed using flow cytometry, and a SA-β-Gal stain was used to observe the senescence ratio of U87 cells following radiation. The expression of Bmi-1 in U87 cells exposed to different doses of radiation was evaluated by western blot analysis. X-ray radiation was found to inhibit U87 cell proliferation through the induction of senescence rather than apoptosis. Following exposure to radiation, the cell cycle distribution was dysregulated, with an increased number of cells in the G2/M phase, and the expression of Bmi-1 was upregulated, particularly when a dose of ≥6 Gy was administered. The results indicated that senescence is the main mechanism by which U87 cell growth is inhibited following radiation. In addition, Bmi-1 may be significant in increasing the radioresistance of glioma cells by enabling cell senescence.

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

“…Cell senescence is characterized by an irreversible cell cycle arrest in G 0 /G 1 phase. In our previous study, in the 6 and 8 Gy groups following 72 h exposure to radiation, the number of senescent cells was markedly increased; however, the number of cells in G 0 /G 1 phase was markedly decreased (17). These results suggest that U-87 MG glioma cells exhibit cellular senescence evasion.…”

“…Furthermore, miRNA-23a is upregulated in glioma and promotes the invasion of glioma cells (16). Our previous study investigated the role of BMI1 polycomb ring finger oncogene (Bmi-1) in the response of U-87 MG cells to radiation exposure (17). The results indicated that miRNA-128a was able to bind to the 3'-UTR of Bmi-1 in order to suppress its expression.…”

“…Our previous study investigated the cell cycle distribution of U-87 MG cells following 72 h exposure to X-ray radiation. The number of cells in G 2 /M phase was significantly increased, and the number of cells in G 0 /G 1 phase were significantly decreased in the 6 and 8 Gy groups (17). Cell senescence is characterized by an irreversible cell cycle arrest in G 0 /G 1 phase.…”

“…In our previous study, the number of U-87 MG glioma cells did not decrease following exposure to various doses of X-ray radiation (17). To investigate whether various X-ray radiation fractions affected cellular growth, the U-87 MG cells were divided into three experimental groups: A conventional group, a hypofraction group, and a superfraction radiation group, which were exposed to X-ray radiation at 2 Gy qd for 5 days, 1.1 bid Gy for 5 days and 8 Gy for 1 day, respectively (Fig.…”

“…These results suggest that X-ray radiation is able to suppress the growth of U-87 MG glioma cells. Our previous study demonstrated that the mechanism underlying radiation inhibition was cellular senescence, as opposed to apoptosis (17).…”