Abstract
Radioresistance severely impedes the treatment of nasopharyngeal carcinoma (NPC). Recent evidence has shown that the abnormal expression of microRNAs (miRNAs) contributes to radiosensitivity. The aim of this study, therefore, was to investigate whether expression of the miRNAs correlated with radiosensitivity in the context of NPC. Quantitative reverse transcription polymerase chain reaction (RT-PCR) was used to quantify miR-451 expression in two representative NPC cell lines. The role of miR-451 in NPC radiosensitivity was analyzed using a colony formation assay and an immunofluorescence assay with overexpression of miR-451 in NPC cells. Luciferase reporter assays, RT-PCR, and Western blot were performed to confirm the target of miR-451. High levels of miR-451 expression enhanced radiosensitivity in NPC cells by inhibiting the repair of irradiation-induced double-strand breaks (DSBs) and increasing apoptosis. The results also demonstrated that miR-451 directly targeted ras-related protein 14 (RAB14). Downregulation of RAB14 partially replicated the miR-451-mediated DSBs induced by ionizing radiation (IR). MiR-451 could be a potential target for enhancing radiosensitivity of NPC cells by targeting RAB14.
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Acknowledgments
We acknowledge the excellent technical support and sincere help of the Functional Genomics and Bioinformatics Cores of Southern Medical University. We also appreciate the language support by Samitha Fernando (Imperial College London, UK). This study was supported by the National Natural Science Foundation of China (81272508), the Specialized Research Fund for the Doctoral Program of Higher Education of China (20114433110015), and the Guangzhou Science and Technology Project Fund (11C22120714).
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Tian Zhang and Quanquan Sun contributed equally to this work.
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Zhang, T., Sun, Q., Liu, T. et al. MiR-451 increases radiosensitivity of nasopharyngeal carcinoma cells by targeting ras-related protein 14 (RAB14). Tumor Biol. 35, 12593–12599 (2014). https://doi.org/10.1007/s13277-014-2581-x
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DOI: https://doi.org/10.1007/s13277-014-2581-x