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Genome-scale CRISPR screening for potential targets of ginsenoside compound K

Ginsenosides exhibit a large variety of biological activities in maintaining physical health; however, the molecule underpinnings underlining these biological activities remain to be defined. Here, we took a cellular condition that compound K (CK) induces autophagic cell death in HeLa cells, and set...

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Autores principales: Yang, Yuanyuan, Liu, Xiaojian, Li, Shuang, Chen, Yanhao, Zhao, Yongxu, Wei, Yuda, Qiu, Yan, Liu, Yan, Zhou, Zhihua, Han, Jun, Wu, Guohao, Ding, Qiurong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6971025/
https://www.ncbi.nlm.nih.gov/pubmed/31959745
http://dx.doi.org/10.1038/s41419-020-2234-5
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author Yang, Yuanyuan
Liu, Xiaojian
Li, Shuang
Chen, Yanhao
Zhao, Yongxu
Wei, Yuda
Qiu, Yan
Liu, Yan
Zhou, Zhihua
Han, Jun
Wu, Guohao
Ding, Qiurong
author_facet Yang, Yuanyuan
Liu, Xiaojian
Li, Shuang
Chen, Yanhao
Zhao, Yongxu
Wei, Yuda
Qiu, Yan
Liu, Yan
Zhou, Zhihua
Han, Jun
Wu, Guohao
Ding, Qiurong
author_sort Yang, Yuanyuan
collection PubMed
description Ginsenosides exhibit a large variety of biological activities in maintaining physical health; however, the molecule underpinnings underlining these biological activities remain to be defined. Here, we took a cellular condition that compound K (CK) induces autophagic cell death in HeLa cells, and setup a high-throughput genetic screening using CRISPR technology. We have identified a number of CK-resistant and CK-sensitive genes, and further validated PMAIP1 as a CK-resistant gene and WASH1 as a CK-sensitive gene. Compound K treatment reduces the expression of WASH1, which further accelerates the autophagic cell death, highlighting WASH1 as an interesting downstream mediator of CK effects. Overall, our study offers an easy-to-adopt platform to study the functional mediators of ginsenosides, and provides a candidate list of genes that are potential targets of CK.
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spelling pubmed-69710252020-01-22 Genome-scale CRISPR screening for potential targets of ginsenoside compound K Yang, Yuanyuan Liu, Xiaojian Li, Shuang Chen, Yanhao Zhao, Yongxu Wei, Yuda Qiu, Yan Liu, Yan Zhou, Zhihua Han, Jun Wu, Guohao Ding, Qiurong Cell Death Dis Article Ginsenosides exhibit a large variety of biological activities in maintaining physical health; however, the molecule underpinnings underlining these biological activities remain to be defined. Here, we took a cellular condition that compound K (CK) induces autophagic cell death in HeLa cells, and setup a high-throughput genetic screening using CRISPR technology. We have identified a number of CK-resistant and CK-sensitive genes, and further validated PMAIP1 as a CK-resistant gene and WASH1 as a CK-sensitive gene. Compound K treatment reduces the expression of WASH1, which further accelerates the autophagic cell death, highlighting WASH1 as an interesting downstream mediator of CK effects. Overall, our study offers an easy-to-adopt platform to study the functional mediators of ginsenosides, and provides a candidate list of genes that are potential targets of CK. Nature Publishing Group UK 2020-01-20 /pmc/articles/PMC6971025/ /pubmed/31959745 http://dx.doi.org/10.1038/s41419-020-2234-5 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Yang, Yuanyuan
Liu, Xiaojian
Li, Shuang
Chen, Yanhao
Zhao, Yongxu
Wei, Yuda
Qiu, Yan
Liu, Yan
Zhou, Zhihua
Han, Jun
Wu, Guohao
Ding, Qiurong
Genome-scale CRISPR screening for potential targets of ginsenoside compound K
title Genome-scale CRISPR screening for potential targets of ginsenoside compound K
title_full Genome-scale CRISPR screening for potential targets of ginsenoside compound K
title_fullStr Genome-scale CRISPR screening for potential targets of ginsenoside compound K
title_full_unstemmed Genome-scale CRISPR screening for potential targets of ginsenoside compound K
title_short Genome-scale CRISPR screening for potential targets of ginsenoside compound K
title_sort genome-scale crispr screening for potential targets of ginsenoside compound k
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6971025/
https://www.ncbi.nlm.nih.gov/pubmed/31959745
http://dx.doi.org/10.1038/s41419-020-2234-5
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