title: 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.
authors.affiliation: Cancer Center, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
authors.forename: Lan
authors.initials: L
authors.lastname: Ye
authors.affiliation: Department of Surgery, Jinan Central Hospital, Jinan, Shandong 250014, P.R. China.
authors.forename: Guanying
authors.initials: G
authors.lastname: Yu
authors.affiliation: Cancer Center, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
authors.forename: Cuihong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Surgery, Jinan Central Hospital, Jinan, Shandong 250014, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Du
authors.affiliation: Cancer Center, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
authors.forename: Dianshui
authors.initials: D
authors.lastname: Sun
authors.affiliation: Cancer Center, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
authors.forename: Junli
authors.initials: J
authors.lastname: Liu
authors.affiliation: Cancer Center, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
authors.forename: Tonggang
authors.initials: T
authors.lastname: Qi
authors.affiliation: Cancer Center, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Yu
authors.affiliation: Cancer Center, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: Cancer Center, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Cancer Center, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D017209:Apoptosis / Q000528:radiation effects; D002453:Cell Cycle; D045744:Cell Line, Tumor / Q000528:radiation effects; D049109:Cell Proliferation / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D015536:Down-Regulation; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D063150:Polycomb Repressive Complex 1 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011836:Radiation Tolerance; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D014965:X-Rays
chemical_list: C069077:BMI1 protein, human; C545189:MIRN128 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D063150:Polycomb Repressive Complex 1