title: Inhibition of Beclin-1-Mediated Autophagy by MicroRNA-17-5p Enhanced the Radiosensitivity of Glioma Cells.
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.
authors.affiliation: Department of Neurology, The First Hospital of Jilin UniversityChangchun, Jilin ProvinceP.R. China.
authors.forename: Weichen
authors.initials: W
authors.lastname: Hou
authors.affiliation: Department of Respiratory Medicine, The First Hospital of Jilin UniversityChangchun, Jilin ProvinceP.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Song
authors.affiliation: Department of Neurology, The First Hospital of Jilin UniversityChangchun, Jilin ProvinceP.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Neurology, The First Hospital of Jilin UniversityChangchun, Jilin ProvinceP.R. China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Neurotrauma, The First Hospital of Jilin UniversityChangchun, Jilin ProvinceP.R. China.
authors.forename: Shuyan
authors.initials: S
authors.lastname: Zhang
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000235:genetics*; D000071186:Beclin-1 / Q000235:genetics*; D001665:Binding Sites; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D005910:Glioma / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D006801:Humans; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D011836:Radiation Tolerance / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: D020413:3' Untranslated Regions; D000071186:Beclin-1; C524941:MIRN17 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering