Upregulation of miR-96 promotes radioresistance in glioblastoma cells via targeting PDCD4

Guo,Pin; Yu,Yanan; Tian,Zibin; Lin,Yingying; Qiu,Yongming; Yao,Weicheng; Zhang,Lijuan

doi:10.3892/ijo.2018.4498

Upregulation of miR-96 promotes radioresistance in glioblastoma cells via targeting PDCD4

Authors:
- Pin Guo
- Yanan Yu
- Zibin Tian
- Yingying Lin
- Yongming Qiu
- Weicheng Yao
- Lijuan Zhang
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Affiliations: Department of Neurosurgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China, Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China, Department of Neurosurgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, P.R. China, Institute of Cerebrovascular Diseases, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China
Published online on: July 23, 2018 https://doi.org/10.3892/ijo.2018.4498
Pages: 1591-1600

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Abstract

Glioblastoma multiforme (GBM) is the most deadly brain tumor, and it is characterized by extremely poor therapeutic response and overall survival. Adjuvant radiotherapy remains the standard of care following surgical resection. Thus, elucidating the mechanisms conferring radioresistance in GBM is extremely urgent. In the present study, miR-96 was demonstrated to be significantly upregulated in radioresistant GBM cells. Knockdown of miR-96 in the radioresistant GBM cells T98G elevated the % of apoptotic cells and reduced their clonogenic formation ability following radiotherapy. By contrast, overexpression of miR-96 in the radiosensitive GBM cells U87-MG reduced the % of apoptotic cells and increased their clonogenic formation ability following radiotherapy. Results from phosphorylated-H2A histone family member X (γH2AX) foci staining and comet assays revealed that miR-96 enhanced the DNA repair processes. Furthermore, miR-96 overexpression conferred radioresistance by downregulating programmed cell death protein 4 (PDCD4). Luciferase assay results revealed that miR-96 bound to the 3'UTR of PDCD4 mRNA. Finally, U87-MG cells regained radiosensitivity following PDCD4 overexpression. Taken together, the present is the first study to establish that upregulation of miR-96 in GBM cells confers radioresistance via targeting PDCD4, which might be a potential therapeutic target for GBM.

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