Abstract
Purpose
This study aimed to investigate the effects of activating transcription factor-5 (ATF5) on nasopharyngeal carcinoma (NPC) cell radioresistance.
Methods
HONE-1 nasopharyngeal carcinoma cells were irradiated by conventional fractionation to generate HONE-1R radiotherapy-resistant cells. Short hairpin RNA (shRNA) expression plasmids targeting the ATF5 gene were constructed and transfected into the HONE-1R cell line. The proliferation assay, colony formation analysis, Transwell Boyden chamber assay and other experimental methods were performed to verify changes in the radiosensitivity and other biological of NPC cells.
Results
X-ray irradiation significantly promoted the upregulation of ATF5 protein levels in HONE-1 cells, and the protein expression of ATF5 increased with the dose of X-ray irradiation (p < 0.05). The colony formation rate, cell survival rate and migration ability of HONE-1R cells were significantly higher than those of HONE-1 cells (p < 0.05). Simultaneously, X-ray could also promote the morphology of epithelial-mesenchymal transition (EMT) in HONE-1 cells, inducing a lower expression level of E-cadherin and a higher expression level of N-cadherin in a dose-dependent manner (p < 0.05). Inhibiting ATF5 significantly reduced the colony formation rate, cell survival rate, migration and invasiveness of HONE-1R cells (p < 0.05). Moreover, sensitizing HONE-1R cells to X-ray irradiation significantly upregulated the expression of E-cadherin and downregulated the expression of N-cadherin in these cells (p < 0.05).
Conclusions
ATF5 may be a potential therapeutic target to improve radiosensitivity in NPC.
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Data availability
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Change history
19 May 2020
The article ATF5 involved in radioresistance in nasopharyngeal carcinoma by promoting epithelial-to-mesenchymal phenotype transition, written by Yu Shuai, Erxi Fan, Qiuyue Zhong, Guangyong Feng, Qiying Chen, Xiaoxia Gou, Guihai Zhang, was originally published.
Abbreviations
- NPC:
-
Nasopharyngeal carcinoma
- ATF5:
-
Activating transcription factor-5
- DAB:
-
Diaminobenzidine
- shRNA:
-
Short hairpin RNA
- DAPI:
-
4′-6-Diamidino-2-phenylindole
- FBS:
-
Foetal bovine serum
- IMRT:
-
Intensity-modulated radiation therapy
- EMT:
-
Epithelial-mesenchymal transition
- MRLC:
-
Myosin regulatory light chain
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Acknowledgements
This work was supported by the National Natural Science Foundation funding Project.
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National Natural Science Foundation funding Project (Number: 81260370).
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Guihai developed and planned the study. Yu, Erxi and Qiuyue performed the irradiation and were responsible for management of the cells. Yu, Erxi and Guangyong performed the experiments and Analyzed the data. All authors participated drafted the manuscript. All authors read and approved the final manuscript.
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Ethical approval this study was approved by the Affiliated Hospital of Zunyi Medical University institutional review board (IRB).
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The original version of this article was revised due to the retrospective open access cancellation request.
The original version of this article was revised due to retrospective open access cancellation order.
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Shuai, Y., Fan, E., Zhong, Q. et al. ATF5 involved in radioresistance in nasopharyngeal carcinoma by promoting epithelial-to-mesenchymal phenotype transition. Eur Arch Otorhinolaryngol 277, 2869–2879 (2020). https://doi.org/10.1007/s00405-020-05996-8
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DOI: https://doi.org/10.1007/s00405-020-05996-8