Open Access
ARTICLE
Inhibition of Beclin-1-Mediated Autophagy by MicroRNA-17-5p Enhanced the Radiosensitivity of Glioma Cells
Weichen Hou*, Lei Song†, Yang Zhao*, Qun Liu*, Shuyan Zhang‡
* Department of Neurology, The First Hospital of Jilin University, Changchun, Jilin Province, P.R. China
† Department of Respiratory Medicine, The First Hospital of Jilin University, Changchun, Jilin Province, P.R. China
‡ Department of Neurotrauma, The First Hospital of Jilin University, Changchun, Jilin Province, P.R. China
Oncology Research 2017, 25(1), 43-53. https://doi.org/10.3727/096504016X14719078133285
Abstract
The role of miRNAs in the radiosensitivity of glioma cells and the underlying mechanism is still far from
clear. In the present study, we detected six downregulated and seven upregulated miRNAs in the serum after
radiotherapy compared with paired serum samples before radiotherapy via miRNA panel PCR. Among these,
miR-17-5p was highly reduced (fold change = −4.21). Further, we validated the levels of miR-17-5p in all
serum samples with qRT-PCR. In addition, statistical analysis suggested that a reduced miR-17-5P level was
positively associated with advanced clinical stage of glioma, incidence of relapse, and tumor differentiation.
Moreover, we provided evidence that irradiation markedly activated autophagy and decreased miR-17-5p in
the glioma cell line. Further, we demonstrated that irradiation-induced autophagy activation was mediated by
beclin-1, and downregulation of beclin-1 via siRNA significantly abolished the irradiation-activated autophagy.
Interestingly, we demonstrated that miR-17-5p could directly target beclin-1 via luciferase gene reporter assay.
Exotic expression of miRNA-17-5p decreased autophagy activity in vitro. In nude mice, miRNA-17-5p upregulation sensitized the xenograft tumor to irradiation and suppressed irradiation-induced autophagy. Finally,
pharmacal inhibition of autophagy markedly enhanced the cytotoxicity of irradiation in RR-U87 cells.
Keywords
Cite This Article
APA Style
Hou, W., Song, L., Zhao, Y., Liu, Q., Zhang, S. (2017). Inhibition of beclin-1-mediated autophagy by microrna-17-5p enhanced the radiosensitivity of glioma cells. Oncology Research, 25(1), 43-53. https://doi.org/10.3727/096504016X14719078133285
Vancouver Style
Hou W, Song L, Zhao Y, Liu Q, Zhang S. Inhibition of beclin-1-mediated autophagy by microrna-17-5p enhanced the radiosensitivity of glioma cells. Oncol Res. 2017;25(1):43-53 https://doi.org/10.3727/096504016X14719078133285
IEEE Style
W. Hou, L. Song, Y. Zhao, Q. Liu, and S. Zhang "Inhibition of Beclin-1-Mediated Autophagy by MicroRNA-17-5p Enhanced the Radiosensitivity of Glioma Cells," Oncol. Res., vol. 25, no. 1, pp. 43-53. 2017. https://doi.org/10.3727/096504016X14719078133285