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Transcriptome analysis uncovers the key pathways and candidate genes related to the treatment of Echinococcus granulosus protoscoleces with the repurposed drug pyronaridine

BACKGROUND: Cystic echinococcosis (CE) is a life-threatening zoonosis caused by the larval form of Echinococcus granulosus tapeworm. Our previous study showed that an approved drug pyronaridine (PND) is highly effective against CE, both in vitro and in an animal model. To identify possible target ge...

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Autores principales: Yu, Yingfang, Li, Jun, Wang, Weisi, Wang, Tian, Qi, Wenjing, Zheng, Xueting, Duan, Lei, Chen, Jiaxu, Li, Shizhu, Han, Xiumin, Zhang, Wenbao, Duan, Liping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276484/
https://www.ncbi.nlm.nih.gov/pubmed/34256697
http://dx.doi.org/10.1186/s12864-021-07875-w
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author Yu, Yingfang
Li, Jun
Wang, Weisi
Wang, Tian
Qi, Wenjing
Zheng, Xueting
Duan, Lei
Chen, Jiaxu
Li, Shizhu
Han, Xiumin
Zhang, Wenbao
Duan, Liping
author_facet Yu, Yingfang
Li, Jun
Wang, Weisi
Wang, Tian
Qi, Wenjing
Zheng, Xueting
Duan, Lei
Chen, Jiaxu
Li, Shizhu
Han, Xiumin
Zhang, Wenbao
Duan, Liping
author_sort Yu, Yingfang
collection PubMed
description BACKGROUND: Cystic echinococcosis (CE) is a life-threatening zoonosis caused by the larval form of Echinococcus granulosus tapeworm. Our previous study showed that an approved drug pyronaridine (PND) is highly effective against CE, both in vitro and in an animal model. To identify possible target genes, transcriptome analysis was performed with E. granulosus sensu stricto protoscoleces treated with PND. RESULTS: A total of 1,321 genes were differentially expressed in protoscoleces treated with PND, including 541 upregulated and 780 downregulated genes. Gene ontology and KEGG analyses revealed that the spliceosome, mitogen-activated protein kinase (MAPK) pathway and ATP-binding cassette (ABC) transporters were the top three enriched pathways. Western blot analysis showed that PND treatment resulted in a dose-dependent increase in protein expression levels of EgMKK1 (MKK3/6-like) and EgMKK2 (MEK1/2-like), two members of MAPK cascades. Interestingly, several heat shock protein (HSP) genes were greatly downregulated including stress-inducible HSPs and their constitutive cognates, and some of them belong to Echinococcus-specific expansion of HSP70. CONCLUSIONS: PND has a great impact on the spliceosome, MAPK pathway and ABC transporters, which may underline the mechanisms by which PND kills E. granulosus protoscoleces. In addition, PND downregulates HSPs expression, suggesting a close relationship between the drug and HSPs. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12864-021-07875-w.
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spelling pubmed-82764842021-07-14 Transcriptome analysis uncovers the key pathways and candidate genes related to the treatment of Echinococcus granulosus protoscoleces with the repurposed drug pyronaridine Yu, Yingfang Li, Jun Wang, Weisi Wang, Tian Qi, Wenjing Zheng, Xueting Duan, Lei Chen, Jiaxu Li, Shizhu Han, Xiumin Zhang, Wenbao Duan, Liping BMC Genomics Research Article BACKGROUND: Cystic echinococcosis (CE) is a life-threatening zoonosis caused by the larval form of Echinococcus granulosus tapeworm. Our previous study showed that an approved drug pyronaridine (PND) is highly effective against CE, both in vitro and in an animal model. To identify possible target genes, transcriptome analysis was performed with E. granulosus sensu stricto protoscoleces treated with PND. RESULTS: A total of 1,321 genes were differentially expressed in protoscoleces treated with PND, including 541 upregulated and 780 downregulated genes. Gene ontology and KEGG analyses revealed that the spliceosome, mitogen-activated protein kinase (MAPK) pathway and ATP-binding cassette (ABC) transporters were the top three enriched pathways. Western blot analysis showed that PND treatment resulted in a dose-dependent increase in protein expression levels of EgMKK1 (MKK3/6-like) and EgMKK2 (MEK1/2-like), two members of MAPK cascades. Interestingly, several heat shock protein (HSP) genes were greatly downregulated including stress-inducible HSPs and their constitutive cognates, and some of them belong to Echinococcus-specific expansion of HSP70. CONCLUSIONS: PND has a great impact on the spliceosome, MAPK pathway and ABC transporters, which may underline the mechanisms by which PND kills E. granulosus protoscoleces. In addition, PND downregulates HSPs expression, suggesting a close relationship between the drug and HSPs. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12864-021-07875-w. BioMed Central 2021-07-13 /pmc/articles/PMC8276484/ /pubmed/34256697 http://dx.doi.org/10.1186/s12864-021-07875-w Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Yu, Yingfang
Li, Jun
Wang, Weisi
Wang, Tian
Qi, Wenjing
Zheng, Xueting
Duan, Lei
Chen, Jiaxu
Li, Shizhu
Han, Xiumin
Zhang, Wenbao
Duan, Liping
Transcriptome analysis uncovers the key pathways and candidate genes related to the treatment of Echinococcus granulosus protoscoleces with the repurposed drug pyronaridine
title Transcriptome analysis uncovers the key pathways and candidate genes related to the treatment of Echinococcus granulosus protoscoleces with the repurposed drug pyronaridine
title_full Transcriptome analysis uncovers the key pathways and candidate genes related to the treatment of Echinococcus granulosus protoscoleces with the repurposed drug pyronaridine
title_fullStr Transcriptome analysis uncovers the key pathways and candidate genes related to the treatment of Echinococcus granulosus protoscoleces with the repurposed drug pyronaridine
title_full_unstemmed Transcriptome analysis uncovers the key pathways and candidate genes related to the treatment of Echinococcus granulosus protoscoleces with the repurposed drug pyronaridine
title_short Transcriptome analysis uncovers the key pathways and candidate genes related to the treatment of Echinococcus granulosus protoscoleces with the repurposed drug pyronaridine
title_sort transcriptome analysis uncovers the key pathways and candidate genes related to the treatment of echinococcus granulosus protoscoleces with the repurposed drug pyronaridine
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276484/
https://www.ncbi.nlm.nih.gov/pubmed/34256697
http://dx.doi.org/10.1186/s12864-021-07875-w
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