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Radiation induces epithelial to mesenchymal transition via upregulation of PD-L1 in nasopharyngeal carcinoma cell

BACKGROUND: The acquisition of radioresistance by nasopharyngeal carcinoma (NPC) cells during radiotherapy may lead to tumor metastasis and poor survival. This study aimed to explore the mechanism of long-term radiation-induced NPC metastasis. METHODS: The radioresistant NPC cell, Hone-1R, was estab...

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Autores principales: Li, Heming, Wang, Zhi, Liang, Shanshan, Liu, Qiuge, Wang, Piao, Cai, Longyu, Wang, Ruoyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8797608/
https://www.ncbi.nlm.nih.gov/pubmed/35116267
http://dx.doi.org/10.21037/tcr-20-1899
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author Li, Heming
Wang, Zhi
Liang, Shanshan
Liu, Qiuge
Wang, Piao
Cai, Longyu
Wang, Ruoyu
author_facet Li, Heming
Wang, Zhi
Liang, Shanshan
Liu, Qiuge
Wang, Piao
Cai, Longyu
Wang, Ruoyu
author_sort Li, Heming
collection PubMed
description BACKGROUND: The acquisition of radioresistance by nasopharyngeal carcinoma (NPC) cells during radiotherapy may lead to tumor metastasis and poor survival. This study aimed to explore the mechanism of long-term radiation-induced NPC metastasis. METHODS: The radioresistant NPC cell, Hone-1R, was established for further study. A colony-forming assay was selected for the evaluation of radioresistant capacity, while a scratch wound healing assay was used to detect tumor cell migration. The expression of relative protein levels were detected by Western blot (WB) analysis and immunofluorescence. Cell morphology was acquired by microscopy. The programmed cell death ligand-1 (PD-L1) expression level in NPC tumor tissues was evaluated based on the publicly available datasets of NPC patients. RESULTS: A radioresistant NPC cell, Hone-1R, was established with a total dose of 180 Gy, and verified by radioresistant capacity testing. The morphology of Hone-1R cells showed obvious mesenchymal-like cells. WB and wound healing assays indicated that Hone-1R cells exhibited an epithelial-mesenchymal transition (EMT) phenotype with high migration ability and upregulation of PD-L1. Knockdown of PD-L1 reversed EMT status and reduced the migration ability of Hone-1R cells. Further analysis indicated that PD-L1 was overexpressed in more advanced stages and was positively correlated with the EMT score in NPC patients based on in silico analysis. CONCLUSIONS: Our study revealed that long-term radiation induces EMT and increases migration ability of NPC radioresistant cells through upregulation of PD-L1. These results advance our investigation of the underlying mechanism of ionizing radiation (IR)-induced migration, and suggest potential interventions to reverse EMT-induced acquisition of radioresistance in NPC.
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spelling pubmed-87976082022-02-02 Radiation induces epithelial to mesenchymal transition via upregulation of PD-L1 in nasopharyngeal carcinoma cell Li, Heming Wang, Zhi Liang, Shanshan Liu, Qiuge Wang, Piao Cai, Longyu Wang, Ruoyu Transl Cancer Res Original Article BACKGROUND: The acquisition of radioresistance by nasopharyngeal carcinoma (NPC) cells during radiotherapy may lead to tumor metastasis and poor survival. This study aimed to explore the mechanism of long-term radiation-induced NPC metastasis. METHODS: The radioresistant NPC cell, Hone-1R, was established for further study. A colony-forming assay was selected for the evaluation of radioresistant capacity, while a scratch wound healing assay was used to detect tumor cell migration. The expression of relative protein levels were detected by Western blot (WB) analysis and immunofluorescence. Cell morphology was acquired by microscopy. The programmed cell death ligand-1 (PD-L1) expression level in NPC tumor tissues was evaluated based on the publicly available datasets of NPC patients. RESULTS: A radioresistant NPC cell, Hone-1R, was established with a total dose of 180 Gy, and verified by radioresistant capacity testing. The morphology of Hone-1R cells showed obvious mesenchymal-like cells. WB and wound healing assays indicated that Hone-1R cells exhibited an epithelial-mesenchymal transition (EMT) phenotype with high migration ability and upregulation of PD-L1. Knockdown of PD-L1 reversed EMT status and reduced the migration ability of Hone-1R cells. Further analysis indicated that PD-L1 was overexpressed in more advanced stages and was positively correlated with the EMT score in NPC patients based on in silico analysis. CONCLUSIONS: Our study revealed that long-term radiation induces EMT and increases migration ability of NPC radioresistant cells through upregulation of PD-L1. These results advance our investigation of the underlying mechanism of ionizing radiation (IR)-induced migration, and suggest potential interventions to reverse EMT-induced acquisition of radioresistance in NPC. AME Publishing Company 2021-01 /pmc/articles/PMC8797608/ /pubmed/35116267 http://dx.doi.org/10.21037/tcr-20-1899 Text en 2021 Translational Cancer Research. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
spellingShingle Original Article
Li, Heming
Wang, Zhi
Liang, Shanshan
Liu, Qiuge
Wang, Piao
Cai, Longyu
Wang, Ruoyu
Radiation induces epithelial to mesenchymal transition via upregulation of PD-L1 in nasopharyngeal carcinoma cell
title Radiation induces epithelial to mesenchymal transition via upregulation of PD-L1 in nasopharyngeal carcinoma cell
title_full Radiation induces epithelial to mesenchymal transition via upregulation of PD-L1 in nasopharyngeal carcinoma cell
title_fullStr Radiation induces epithelial to mesenchymal transition via upregulation of PD-L1 in nasopharyngeal carcinoma cell
title_full_unstemmed Radiation induces epithelial to mesenchymal transition via upregulation of PD-L1 in nasopharyngeal carcinoma cell
title_short Radiation induces epithelial to mesenchymal transition via upregulation of PD-L1 in nasopharyngeal carcinoma cell
title_sort radiation induces epithelial to mesenchymal transition via upregulation of pd-l1 in nasopharyngeal carcinoma cell
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8797608/
https://www.ncbi.nlm.nih.gov/pubmed/35116267
http://dx.doi.org/10.21037/tcr-20-1899
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