Cargando…
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...
Autores principales: | , , , , , , , , , , , |
---|---|
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 |
_version_ | 1783721913748553728 |
---|---|
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. |
format | Online Article Text |
id | pubmed-8276484 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT yuyingfang transcriptomeanalysisuncoversthekeypathwaysandcandidategenesrelatedtothetreatmentofechinococcusgranulosusprotoscoleceswiththerepurposeddrugpyronaridine AT lijun transcriptomeanalysisuncoversthekeypathwaysandcandidategenesrelatedtothetreatmentofechinococcusgranulosusprotoscoleceswiththerepurposeddrugpyronaridine AT wangweisi transcriptomeanalysisuncoversthekeypathwaysandcandidategenesrelatedtothetreatmentofechinococcusgranulosusprotoscoleceswiththerepurposeddrugpyronaridine AT wangtian transcriptomeanalysisuncoversthekeypathwaysandcandidategenesrelatedtothetreatmentofechinococcusgranulosusprotoscoleceswiththerepurposeddrugpyronaridine AT qiwenjing transcriptomeanalysisuncoversthekeypathwaysandcandidategenesrelatedtothetreatmentofechinococcusgranulosusprotoscoleceswiththerepurposeddrugpyronaridine AT zhengxueting transcriptomeanalysisuncoversthekeypathwaysandcandidategenesrelatedtothetreatmentofechinococcusgranulosusprotoscoleceswiththerepurposeddrugpyronaridine AT duanlei transcriptomeanalysisuncoversthekeypathwaysandcandidategenesrelatedtothetreatmentofechinococcusgranulosusprotoscoleceswiththerepurposeddrugpyronaridine AT chenjiaxu transcriptomeanalysisuncoversthekeypathwaysandcandidategenesrelatedtothetreatmentofechinococcusgranulosusprotoscoleceswiththerepurposeddrugpyronaridine AT lishizhu transcriptomeanalysisuncoversthekeypathwaysandcandidategenesrelatedtothetreatmentofechinococcusgranulosusprotoscoleceswiththerepurposeddrugpyronaridine AT hanxiumin transcriptomeanalysisuncoversthekeypathwaysandcandidategenesrelatedtothetreatmentofechinococcusgranulosusprotoscoleceswiththerepurposeddrugpyronaridine AT zhangwenbao transcriptomeanalysisuncoversthekeypathwaysandcandidategenesrelatedtothetreatmentofechinococcusgranulosusprotoscoleceswiththerepurposeddrugpyronaridine AT duanliping transcriptomeanalysisuncoversthekeypathwaysandcandidategenesrelatedtothetreatmentofechinococcusgranulosusprotoscoleceswiththerepurposeddrugpyronaridine |