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Targeting programmed cell death ligand 1 by CRISPR/Cas9 in osteosarcoma cells
Programmed cell death ligand 1 (PD-L1) is a transmembrane protein that is expressed on tumor cells that suppresses the T cell-mediated immune response. Therapies targeting the PD-L1 pathway promote anti-tumor immunity and have shown promising results in some types of cancers. However, the functional...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5444742/ https://www.ncbi.nlm.nih.gov/pubmed/28415820 http://dx.doi.org/10.18632/oncotarget.16326 |
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author | Liao, Yunfei Chen, Lulu Feng, Yong Shen, Jacson Gao, Yan Cote, Gregory Choy, Edwin Harmon, David Mankin, Henry Hornicek, Francis Duan, Zhenfeng |
author_facet | Liao, Yunfei Chen, Lulu Feng, Yong Shen, Jacson Gao, Yan Cote, Gregory Choy, Edwin Harmon, David Mankin, Henry Hornicek, Francis Duan, Zhenfeng |
author_sort | Liao, Yunfei |
collection | PubMed |
description | Programmed cell death ligand 1 (PD-L1) is a transmembrane protein that is expressed on tumor cells that suppresses the T cell-mediated immune response. Therapies targeting the PD-L1 pathway promote anti-tumor immunity and have shown promising results in some types of cancers. However, the functional and therapeutic roles of PD-L1 in osteosarcoma remain largely unknown. In this study, we found that PD-L1 protein was expressed in osteosarcoma cell lines and tissue microarray of patient tumors. Tissue microarray immunohistochemistry analysis showed that the overall and five-year survival rates of patients with high levels of PD-L1 expression were significantly shorter than patients with low levels. High levels of PD-L1 expression were also associated with metastasis in osteosarcoma patients. Furthermore, we applied the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 system to target PD-L1 gene at the DNA level in osteosarcoma cell lines. We found that the expression of PD-L1 could be efficiently disrupted by CRISPR/Cas9 system and PD-L1 knockdown increased drug sensitivities for doxorubicin and paclitaxel. These results suggest that PD-L1 is an independent prognostic factor in osteosarcoma and that PD-L1 knockout by CRISPR/Cas9 may be a therapeutic approach for the treatment of osteosarcoma. |
format | Online Article Text |
id | pubmed-5444742 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-54447422017-06-01 Targeting programmed cell death ligand 1 by CRISPR/Cas9 in osteosarcoma cells Liao, Yunfei Chen, Lulu Feng, Yong Shen, Jacson Gao, Yan Cote, Gregory Choy, Edwin Harmon, David Mankin, Henry Hornicek, Francis Duan, Zhenfeng Oncotarget Research Paper Programmed cell death ligand 1 (PD-L1) is a transmembrane protein that is expressed on tumor cells that suppresses the T cell-mediated immune response. Therapies targeting the PD-L1 pathway promote anti-tumor immunity and have shown promising results in some types of cancers. However, the functional and therapeutic roles of PD-L1 in osteosarcoma remain largely unknown. In this study, we found that PD-L1 protein was expressed in osteosarcoma cell lines and tissue microarray of patient tumors. Tissue microarray immunohistochemistry analysis showed that the overall and five-year survival rates of patients with high levels of PD-L1 expression were significantly shorter than patients with low levels. High levels of PD-L1 expression were also associated with metastasis in osteosarcoma patients. Furthermore, we applied the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 system to target PD-L1 gene at the DNA level in osteosarcoma cell lines. We found that the expression of PD-L1 could be efficiently disrupted by CRISPR/Cas9 system and PD-L1 knockdown increased drug sensitivities for doxorubicin and paclitaxel. These results suggest that PD-L1 is an independent prognostic factor in osteosarcoma and that PD-L1 knockout by CRISPR/Cas9 may be a therapeutic approach for the treatment of osteosarcoma. Impact Journals LLC 2017-03-17 /pmc/articles/PMC5444742/ /pubmed/28415820 http://dx.doi.org/10.18632/oncotarget.16326 Text en Copyright: © 2017 Liao et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Research Paper Liao, Yunfei Chen, Lulu Feng, Yong Shen, Jacson Gao, Yan Cote, Gregory Choy, Edwin Harmon, David Mankin, Henry Hornicek, Francis Duan, Zhenfeng Targeting programmed cell death ligand 1 by CRISPR/Cas9 in osteosarcoma cells |
title | Targeting programmed cell death ligand 1 by CRISPR/Cas9 in osteosarcoma cells |
title_full | Targeting programmed cell death ligand 1 by CRISPR/Cas9 in osteosarcoma cells |
title_fullStr | Targeting programmed cell death ligand 1 by CRISPR/Cas9 in osteosarcoma cells |
title_full_unstemmed | Targeting programmed cell death ligand 1 by CRISPR/Cas9 in osteosarcoma cells |
title_short | Targeting programmed cell death ligand 1 by CRISPR/Cas9 in osteosarcoma cells |
title_sort | targeting programmed cell death ligand 1 by crispr/cas9 in osteosarcoma cells |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5444742/ https://www.ncbi.nlm.nih.gov/pubmed/28415820 http://dx.doi.org/10.18632/oncotarget.16326 |
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