A high-throughput screening identifies microRNA inhibitors that influence neuronal maintenance and/or response to oxidative stress

Small non-coding RNAs (sncRNAs), including microRNAs (miRNAs) are important post-transcriptional gene expression regulators relevant in physiological and pathological processes. Here, we combined a high-throughput functional screening (HTFS) platform with a library of antisense oligonucleotides (ASO...

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Autores: Pallarès Albanell, Joan, 1988-, Zomeño-Abellán, M. Teresa, Escaramís, Geòrgia, Pantano Rubiño, Lorena, 1982-, Soriano, Aroa, Segura, Miguel F., Martí, Eulàlia
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/44122
Acceso en línea:http://hdl.handle.net/10230/44122
http://dx.doi.org/10.1016/j.omtn.2019.06.007
Access Level:acceso abierto
Palabra clave:Expression profiles
High-throughput screening
miRNAs
Mitochondrial function
Neurodegeneration
Non-coding RNAs
Oxidative stress
Small RNA sequencing
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spelling A high-throughput screening identifies microRNA inhibitors that influence neuronal maintenance and/or response to oxidative stressPallarès Albanell, Joan, 1988-Zomeño-Abellán, M. TeresaEscaramís, GeòrgiaPantano Rubiño, Lorena, 1982-Soriano, AroaSegura, Miguel F.Martí, EulàliaExpression profilesHigh-throughput screeningmiRNAsMitochondrial functionNeurodegenerationNon-coding RNAsOxidative stressSmall RNA sequencingSmall non-coding RNAs (sncRNAs), including microRNAs (miRNAs) are important post-transcriptional gene expression regulators relevant in physiological and pathological processes. Here, we combined a high-throughput functional screening (HTFS) platform with a library of antisense oligonucleotides (ASOs) to systematically identify sncRNAs that affect neuronal cell survival in basal conditions and in response to oxidative stress (OS), a major hallmark in neurodegenerative diseases. We considered hits commonly detected by two statistical methods in three biological replicates. Forty-seven ASOs targeting miRNAs (miRNA-ASOs) consistently decreased cell viability under basal conditions. A total of 60 miRNA-ASOs worsened cell viability impairment mediated by OS, with 36.6% commonly affecting cell viability under basal conditions. In addition, 40 miRNA-ASOs significantly protected neuronal cells from OS. In agreement with cell viability impairment, damaging miRNA-ASOs specifically induced increased free radical biogenesis. miRNAs targeted by the detrimental ASOs are enriched in the fraction of miRNAs downregulated by OS, suggesting that the miRNA expression pattern after OS contributes to neuronal damage. The present HTFS highlighted potentially druggable sncRNAs. However, future studies are needed to define the pathways by which the identified ASOs regulate cell survival and OS response and to explore the potential of translating the current findings into clinical applications.This work was supported by the Spanish Ministry of Economy and Competitiveness and FEDER funds (SAF2014-60551-R and SAF2017-88452-R). We acknowledge the support of the Spanish Ministry of Economy, Industry and Competitiveness (MEIC) to the EMBL partnership and the Centro de Excelencia Severo Ochoa 2013–2017 (SEV-2012-0208). We acknowledge the support of the Spanish Ministry of Science Innovation and Universities, Maria Maeztu Unit of Excellence Programme. We thank the staff of the Genomics Unit for the preparation of sRNA libraries and sequencing and the staff of the Biomolecular Screening and Protein Technologies Unit for their help in the setting up the high-throughput screening.Elsevier202020202019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/44122http://dx.doi.org/10.1016/j.omtn.2019.06.007reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésMol Ther Nucleic Acids. 2019; 17:374-87info:eu-repo/grantAgreement/ES/1PE/SAF2014-60551-Rinfo:eu-repo/grantAgreement/ES/2PE/SAF2017-88452-R© 2019 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10230/441222026-05-29T05:05:01Z
dc.title.none.fl_str_mv A high-throughput screening identifies microRNA inhibitors that influence neuronal maintenance and/or response to oxidative stress
title A high-throughput screening identifies microRNA inhibitors that influence neuronal maintenance and/or response to oxidative stress
spellingShingle A high-throughput screening identifies microRNA inhibitors that influence neuronal maintenance and/or response to oxidative stress
Pallarès Albanell, Joan, 1988-
Expression profiles
High-throughput screening
miRNAs
Mitochondrial function
Neurodegeneration
Non-coding RNAs
Oxidative stress
Small RNA sequencing
title_short A high-throughput screening identifies microRNA inhibitors that influence neuronal maintenance and/or response to oxidative stress
title_full A high-throughput screening identifies microRNA inhibitors that influence neuronal maintenance and/or response to oxidative stress
title_fullStr A high-throughput screening identifies microRNA inhibitors that influence neuronal maintenance and/or response to oxidative stress
title_full_unstemmed A high-throughput screening identifies microRNA inhibitors that influence neuronal maintenance and/or response to oxidative stress
title_sort A high-throughput screening identifies microRNA inhibitors that influence neuronal maintenance and/or response to oxidative stress
dc.creator.none.fl_str_mv Pallarès Albanell, Joan, 1988-
Zomeño-Abellán, M. Teresa
Escaramís, Geòrgia
Pantano Rubiño, Lorena, 1982-
Soriano, Aroa
Segura, Miguel F.
Martí, Eulàlia
author Pallarès Albanell, Joan, 1988-
author_facet Pallarès Albanell, Joan, 1988-
Zomeño-Abellán, M. Teresa
Escaramís, Geòrgia
Pantano Rubiño, Lorena, 1982-
Soriano, Aroa
Segura, Miguel F.
Martí, Eulàlia
author_role author
author2 Zomeño-Abellán, M. Teresa
Escaramís, Geòrgia
Pantano Rubiño, Lorena, 1982-
Soriano, Aroa
Segura, Miguel F.
Martí, Eulàlia
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Expression profiles
High-throughput screening
miRNAs
Mitochondrial function
Neurodegeneration
Non-coding RNAs
Oxidative stress
Small RNA sequencing
topic Expression profiles
High-throughput screening
miRNAs
Mitochondrial function
Neurodegeneration
Non-coding RNAs
Oxidative stress
Small RNA sequencing
description Small non-coding RNAs (sncRNAs), including microRNAs (miRNAs) are important post-transcriptional gene expression regulators relevant in physiological and pathological processes. Here, we combined a high-throughput functional screening (HTFS) platform with a library of antisense oligonucleotides (ASOs) to systematically identify sncRNAs that affect neuronal cell survival in basal conditions and in response to oxidative stress (OS), a major hallmark in neurodegenerative diseases. We considered hits commonly detected by two statistical methods in three biological replicates. Forty-seven ASOs targeting miRNAs (miRNA-ASOs) consistently decreased cell viability under basal conditions. A total of 60 miRNA-ASOs worsened cell viability impairment mediated by OS, with 36.6% commonly affecting cell viability under basal conditions. In addition, 40 miRNA-ASOs significantly protected neuronal cells from OS. In agreement with cell viability impairment, damaging miRNA-ASOs specifically induced increased free radical biogenesis. miRNAs targeted by the detrimental ASOs are enriched in the fraction of miRNAs downregulated by OS, suggesting that the miRNA expression pattern after OS contributes to neuronal damage. The present HTFS highlighted potentially druggable sncRNAs. However, future studies are needed to define the pathways by which the identified ASOs regulate cell survival and OS response and to explore the potential of translating the current findings into clinical applications.
publishDate 2019
dc.date.none.fl_str_mv 2019
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/44122
http://dx.doi.org/10.1016/j.omtn.2019.06.007
url http://hdl.handle.net/10230/44122
http://dx.doi.org/10.1016/j.omtn.2019.06.007
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Mol Ther Nucleic Acids. 2019; 17:374-87
info:eu-repo/grantAgreement/ES/1PE/SAF2014-60551-R
info:eu-repo/grantAgreement/ES/2PE/SAF2017-88452-R
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155

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