Targeting uPAR by CRISPR/Cas9 System Attenuates Cancer Malignancy and Multidrug Resistance

Urokinase plasminogen activator receptor (uPAR), a member of the lymphocyte antigen 6 protein superfamily, is overexpressed in different types of cancers and plays an important role in tumorigenesis and development. In this study, we successfully targeted uPAR by CRISPR/Cas9 system in two human canc...

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Autores principales: Wang, Kun, Xing, Zi-Hao, Jiang, Qi-Wei, Yang, Yang, Huang, Jia-Rong, Yuan, Meng-Ling, Wei, Meng-Ning, Li, Yao, Wang, Sheng-Te, Liu, Kun, Shi, Zhi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Oncology
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6400983/
https://www.ncbi.nlm.nih.gov/pubmed/30873379
http://dx.doi.org/10.3389/fonc.2019.00080
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author Wang, Kun
Xing, Zi-Hao
Jiang, Qi-Wei
Yang, Yang
Huang, Jia-Rong
Yuan, Meng-Ling
Wei, Meng-Ning
Li, Yao
Wang, Sheng-Te
Liu, Kun
Shi, Zhi
author_facet Wang, Kun
Xing, Zi-Hao
Jiang, Qi-Wei
Yang, Yang
Huang, Jia-Rong
Yuan, Meng-Ling
Wei, Meng-Ning
Li, Yao
Wang, Sheng-Te
Liu, Kun
Shi, Zhi
author_sort Wang, Kun
collection PubMed
description Urokinase plasminogen activator receptor (uPAR), a member of the lymphocyte antigen 6 protein superfamily, is overexpressed in different types of cancers and plays an important role in tumorigenesis and development. In this study, we successfully targeted uPAR by CRISPR/Cas9 system in two human cancer cell lines with two individual sgRNAs. Knockout of uPAR inhibited cell proliferation, migration and invasion. Furthermore, knockout of uPAR decreases resistance to 5-FU, cisplatin, docetaxel, and doxorubicin in these cells. Although there are several limitations in the application of CRISPR/Cas9 system for cancer patients, our study offers valuable evidences for the role of uPAR in cancer malignancy and drug resistance.
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spelling pubmed-64009832019-03-14 Targeting uPAR by CRISPR/Cas9 System Attenuates Cancer Malignancy and Multidrug Resistance Wang, Kun Xing, Zi-Hao Jiang, Qi-Wei Yang, Yang Huang, Jia-Rong Yuan, Meng-Ling Wei, Meng-Ning Li, Yao Wang, Sheng-Te Liu, Kun Shi, Zhi Front Oncol Oncology Urokinase plasminogen activator receptor (uPAR), a member of the lymphocyte antigen 6 protein superfamily, is overexpressed in different types of cancers and plays an important role in tumorigenesis and development. In this study, we successfully targeted uPAR by CRISPR/Cas9 system in two human cancer cell lines with two individual sgRNAs. Knockout of uPAR inhibited cell proliferation, migration and invasion. Furthermore, knockout of uPAR decreases resistance to 5-FU, cisplatin, docetaxel, and doxorubicin in these cells. Although there are several limitations in the application of CRISPR/Cas9 system for cancer patients, our study offers valuable evidences for the role of uPAR in cancer malignancy and drug resistance. Frontiers Media S.A. 2019-02-27 /pmc/articles/PMC6400983/ /pubmed/30873379 http://dx.doi.org/10.3389/fonc.2019.00080 Text en Copyright © 2019 Wang, Xing, Jiang, Yang, Huang, Yuan, Wei, Li, Wang, Liu and Shi. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Wang, Kun
Xing, Zi-Hao
Jiang, Qi-Wei
Yang, Yang
Huang, Jia-Rong
Yuan, Meng-Ling
Wei, Meng-Ning
Li, Yao
Wang, Sheng-Te
Liu, Kun
Shi, Zhi
Targeting uPAR by CRISPR/Cas9 System Attenuates Cancer Malignancy and Multidrug Resistance
title Targeting uPAR by CRISPR/Cas9 System Attenuates Cancer Malignancy and Multidrug Resistance
title_full Targeting uPAR by CRISPR/Cas9 System Attenuates Cancer Malignancy and Multidrug Resistance
title_fullStr Targeting uPAR by CRISPR/Cas9 System Attenuates Cancer Malignancy and Multidrug Resistance
title_full_unstemmed Targeting uPAR by CRISPR/Cas9 System Attenuates Cancer Malignancy and Multidrug Resistance
title_short Targeting uPAR by CRISPR/Cas9 System Attenuates Cancer Malignancy and Multidrug Resistance
title_sort targeting upar by crispr/cas9 system attenuates cancer malignancy and multidrug resistance
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6400983/
https://www.ncbi.nlm.nih.gov/pubmed/30873379
http://dx.doi.org/10.3389/fonc.2019.00080
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