title: MicroRNA-138-5p controls sensitivity of nasopharyngeal carcinoma to radiation by targeting EIF4EBP1.
abstract: Radiation therapy is the standard treatment for primary nasopharyngeal carcinoma (NPC). MicroRNA regulates cancer responsiveness to radiation therapy by controlling the genes involved in radiation responses. Recent studies suggested that downregulation of microRNA-138-5p was clinically significant in NPC. Here, we evaluated the effect of miR-138-5p on radiosensitivity of NPC cells and explored the underlying mechanisms by identifying its target gene that impacted sensitivity to radiation. Our results revealed that overexpression of miR-138-5p reduced the ability to form colonies, inhibited proliferation, and enhanced radiation-induced DNA damage and autophagy in NPC cells upon radiation treatment. By integrating predicted targets with the transcripts downregulated by miR-138-5p, EIF4EBP1 was identified to be a target gene of miR-138-5p. Results from luciferase reporter assay demonstrated that miR-138-5p downregulated the expression of EIF4EBP1 by binding to the 3'-UTR. Silence of EIF4EBP1 enhanced radiosensitivity of NPC cells as evidenced by reduced ability to form colonies after radiation exposure. In summary, our results indicated that miR-138-5p enhanced radiosensitivity of NPC cells by targeting EIF4EBP1. Further studies are warranted to investigate the potential use of miR-138-5p in the clinical management and treatment prediction of NPC patients.
authors.affiliation: Department of Surgery, The University of Hong Kong, Hong Kong, SAR, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Gao
authors.affiliation: Department of Surgery, The University of Hong Kong, Hong Kong, SAR, P.R. China.
authors.forename: Jacky Wei Kei
authors.initials: JW
authors.lastname: Lam
authors.affiliation: Department of Surgery, The University of Hong Kong, Hong Kong, SAR, P.R. China.
authors.forename: John Zeng-Hong
authors.initials: JZ
authors.lastname: Li
authors.affiliation: Department of Surgery, The University of Hong Kong, Hong Kong, SAR, P.R. China.
authors.forename: Si-Qi
authors.initials: SQ
authors.lastname: Chen
authors.affiliation: Department of Surgery, The University of Hong Kong, Hong Kong, SAR, P.R. China.
authors.forename: Raymond King-Yin
authors.initials: RK
authors.lastname: Tsang
authors.affiliation: Department of Surgery, The University of Hong Kong, Hong Kong, SAR, P.R. China.
authors.forename: Jimmy Yu-Wai
authors.initials: JY
authors.lastname: Chan
authors.affiliation: Department of Surgery, The University of Hong Kong, Hong Kong, SAR, P.R. China.
authors.forename: Thian-Sze
authors.initials: TS
authors.lastname: Wong
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects; D001343:Autophagy / Q000235:genetics* / Q000528:radiation effects; D018797:Cell Cycle Proteins; D049109:Cell Proliferation / Q000235:genetics* / Q000528:radiation effects; D004249:DNA Damage / Q000235:genetics* / Q000528:radiation effects; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011836:Radiation Tolerance / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; C546110:MIRN138 microRNA, human; D035683:MicroRNAs; D010750:Phosphoproteins