dc.contributor | Vall d'Hebron Barcelona Hospital Campus |
dc.contributor.author | Pallarès-Albanell, Joan |
dc.contributor.author | Zomeño-Abellán, Teresa M |
dc.contributor.author | Escaramís, G |
dc.contributor.author | Pantano, L |
dc.contributor.author | Soriano Fernández, Aroa |
dc.contributor.author | Segura Ginard, Miguel |
dc.date.accessioned | 2020-01-29T08:21:38Z |
dc.date.available | 2020-01-29T08:21:38Z |
dc.date.issued | 2019-06-20 |
dc.identifier.citation | Pallarès-Albanell J, Zomeño-Abellán MT, Escaramís G, Pantano L, Soriano A, Segura MF, et al. 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. |
dc.identifier.issn | 2162-2531 |
dc.identifier.uri | https://hdl.handle.net/11351/4565 |
dc.description | Oxidative stress; Small RNA sequencing; Neurodegeneration |
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.language.iso | eng |
dc.publisher | Elsevier |
dc.relation.ispartofseries | Molecular Therapy Nucleic Acids;17 |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 International |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
dc.source | Scientia |
dc.subject | MicroARN |
dc.subject | Radicals lliures |
dc.subject | Genètica - Tècnica |
dc.subject.mesh | MicroRNAs |
dc.subject.mesh | Oxidative Stress |
dc.subject.mesh | Sequence Analysis, RNA |
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.identifier.doi | 10.1016/j.omtn.2019.06.007 |
dc.subject.decs | microARN |
dc.subject.decs | estrés oxidativo |
dc.subject.decs | análisis de secuencias de ARN |
dc.relation.publishversion | https://www.sciencedirect.com/science/article/pii/S2162253119301702?via%3Dihub |
dc.type.version | info:eu-repo/semantics/publishedVersion |
dc.audience | Professionals |
dc.contributor.authoraffiliation | [Pallarès-Albanell J, Zomeño-Abellán MT] Centre for Genomic Regulation (CRG), The Barcelona Institute for Science and Technology, Barcelona, Spain. [Escaramís G] Centre for Genomic Regulation (CRG), The Barcelona Institute for Science and Technology, Barcelona, Spain. Departament de Biomedicina, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain. Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain. Research Group on Statistics, Econometrics and Health, Universitat de Girona, Girona, Spain. Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Ministerio de Ciencia Innovación y Universidades, Madrid, Spain. [Pantano L] Bioinformatics Core, Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA. [Soriano A, Segura MF] Recerca Translacional en Càncer en la Infància i l'Adolescència, Vall d'Hebron Institut de Recerca, Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain |
dc.identifier.pmid | 31302497 |
dc.identifier.wos | 000487984400032 |
dc.rights.accessrights | info:eu-repo/semantics/openAccess |