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Title: A high-throughput screening identifies microRNA inhibitors that influence neuronal maintenance and/or response to oxidative stress
Author: Pallarès Albanell, Joan
Zomeño Abellán, M. Teresa
Escaramís Babiano, Geòrgia
Pantano, Lorena
Soriano, Aroa
Segura, Miguel F.
Martí Puig, Eulàlia
Keywords: Oligonucleòtids
Malalties neurodegeneratives
Origen de la vida
Neurodegenerative Diseases
Origin of life
Issue Date: 6-Sep-2019
Publisher: Elsevier
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.
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It is part of: Molecular Therapy-Nucleic Acids, 2019, vol. 17, p. 374-387
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ISSN: 2162-2531
Appears in Collections:Articles publicats en revistes (Biomedicina)

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