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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Detalles Bibliográficos
Autores: Pallarès Albanell, Joan, Zomeño Abellán, M. Teresa, Escaramís Babiano, Geòrgia, Pantano, Lorena, 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:10256/18192
Acceso en línea:http://hdl.handle.net/10256/18192
Access Level:acceso abierto
Palabra clave:Econometria
Econometrics
RNA -- Models matemàtics
RNA -- Mathematical models
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spelling A High-Throughput Screening Identifies MicroRNA Inhibitors That Influence Neuronal Maintenance and/or Response to Oxidative StressPallarès Albanell, JoanZomeño Abellán, M. TeresaEscaramís Babiano, GeòrgiaPantano, LorenaSoriano, AroaSegura, Miguel F.Martí, EulàliaEconometriaEconometricsRNA -- Models matemàticsRNA -- Mathematical modelsSmall 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 applicationsAmerican Society of Gene and Cell Therapy2019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionpeer-reviewedapplication/pdfhttp://hdl.handle.net/10256/18192http://hdl.handle.net/10256/18192Molecular Therapy: Nucleic Acids, 2019, vol. 17, p. 374-387Articles publicats (D-EC)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)Inglésinfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.omtn.2019.06.007info:eu-repo/semantics/altIdentifier/issn/2162-2531Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10256/181922026-05-29T05:05:01Z
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
Econometria
Econometrics
RNA -- Models matemàtics
RNA -- Mathematical models
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
Zomeño Abellán, M. Teresa
Escaramís Babiano, Geòrgia
Pantano, Lorena
Soriano, Aroa
Segura, Miguel F.
Martí, Eulàlia
author Pallarès Albanell, Joan
author_facet Pallarès Albanell, Joan
Zomeño Abellán, M. Teresa
Escaramís Babiano, Geòrgia
Pantano, Lorena
Soriano, Aroa
Segura, Miguel F.
Martí, Eulàlia
author_role author
author2 Zomeño Abellán, M. Teresa
Escaramís Babiano, Geòrgia
Pantano, Lorena
Soriano, Aroa
Segura, Miguel F.
Martí, Eulàlia
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Econometria
Econometrics
RNA -- Models matemàtics
RNA -- Mathematical models
topic Econometria
Econometrics
RNA -- Models matemàtics
RNA -- Mathematical models
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
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
peer-reviewed
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10256/18192
http://hdl.handle.net/10256/18192
url http://hdl.handle.net/10256/18192
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.omtn.2019.06.007
info:eu-repo/semantics/altIdentifier/issn/2162-2531
dc.rights.none.fl_str_mv Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Society of Gene and Cell Therapy
publisher.none.fl_str_mv American Society of Gene and Cell Therapy
dc.source.none.fl_str_mv Molecular Therapy: Nucleic Acids, 2019, vol. 17, p. 374-387
Articles publicats (D-EC)
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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