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

Pallarès Albanell, Joan, 1988-; Zomeño-Abellán, M. Teresa; Escaramís, Geòrgia; Pantano Rubiño, Lorena, 1982-; Soriano, Aroa; Segura, Miguel F.; Martí, Eulàlia

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

Mostra el registre complet Registre parcial de l'ítem

dc.contributor.author Pallarès Albanell, Joan, 1988-
dc.contributor.author Zomeño-Abellán, M. Teresa
dc.contributor.author Escaramís, Geòrgia
dc.contributor.author Pantano Rubiño, Lorena, 1982-
dc.contributor.author Soriano, Aroa
dc.contributor.author Segura, Miguel F.
dc.contributor.author Martí, Eulàlia
dc.date.accessioned 2020-03-31T07:46:27Z
dc.date.available 2020-03-31T07:46:27Z
dc.date.issued 2019
dc.description.abstract 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.
dc.description.sponsorship 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.
dc.format.mimetype application/pdf
dc.identifier.citation Pallarès-Albanell J, Zomeño-Abellán MT, Escaramís G, Pantano L, Soriano A, Segura MF, Martí E. A high-throughput screening identifies microRNA inhibitors that influence neuronal maintenance and/or response to oxidative stress. Mol Ther Nucleic Acids. 2019; 17:374-87. DOI: 10.1016/j.omtn.2019.06.007
dc.identifier.doi http://dx.doi.org/10.1016/j.omtn.2019.06.007
dc.identifier.issn 2162-2531
dc.identifier.uri http://hdl.handle.net/10230/44122
dc.language.iso eng
dc.publisher Elsevier
dc.relation.ispartof Mol Ther Nucleic Acids. 2019; 17:374-87
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2014-60551-R
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/SAF2017-88452-R
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.keyword Expression profiles
dc.subject.keyword High-throughput screening
dc.subject.keyword miRNAs
dc.subject.keyword Mitochondrial function
dc.subject.keyword Neurodegeneration
dc.subject.keyword Non-coding RNAs
dc.subject.keyword Oxidative stress
dc.subject.keyword Small RNA sequencing
dc.title A high-throughput screening identifies microRNA inhibitors that influence neuronal maintenance and/or response to oxidative stress
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

Col·leccions

Articles (Center for Genomic Regulation (CRG))