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MicroRNA expression analysis identifies a subset of downregulated miRNAs in ALS motor neuron progenitors
Amyotrophic lateral sclerosis (ALS) is a fatal neurological disorder that is characterized by a progressive degeneration of motor neurons (MNs). The pathomechanism underlying the disease is largely unknown, even though increasing evidence suggests that RNA metabolism, including microRNAs (miRNAs) ma...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6031650/ https://www.ncbi.nlm.nih.gov/pubmed/29973608 http://dx.doi.org/10.1038/s41598-018-28366-1 |
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author | Rizzuti, Mafalda Filosa, Giuseppe Melzi, Valentina Calandriello, Luca Dioni, Laura Bollati, Valentina Bresolin, Nereo Comi, Giacomo Pietro Barabino, Silvia Nizzardo, Monica Corti, Stefania |
author_facet | Rizzuti, Mafalda Filosa, Giuseppe Melzi, Valentina Calandriello, Luca Dioni, Laura Bollati, Valentina Bresolin, Nereo Comi, Giacomo Pietro Barabino, Silvia Nizzardo, Monica Corti, Stefania |
author_sort | Rizzuti, Mafalda |
collection | PubMed |
description | Amyotrophic lateral sclerosis (ALS) is a fatal neurological disorder that is characterized by a progressive degeneration of motor neurons (MNs). The pathomechanism underlying the disease is largely unknown, even though increasing evidence suggests that RNA metabolism, including microRNAs (miRNAs) may play an important role. In this study, human ALS induced pluripotent stem cells were differentiated into MN progenitors and their miRNA expression profiles were compared to those of healthy control cells. We identified 15 downregulated miRNAs in patients’ cells. Gene ontology and molecular pathway enrichment analysis indicated that the predicted target genes of the differentially expressed miRNAs were involved in neurodegeneration-related pathways. Among the 15 examined miRNAs, miR-34a and miR504 appeared particularly relevant due to their involvement in the p53 pathway, synaptic vesicle regulation and general involvement in neurodegenerative diseases. Taken together our results demonstrate that the neurodegenerative phenotype in ALS can be associated with a dysregulation of miRNAs involved in the control of disease-relevant genetic pathways, suggesting that targeting entire gene networks can be a potential strategy to treat complex diseases such as ALS. |
format | Online Article Text |
id | pubmed-6031650 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-60316502018-07-12 MicroRNA expression analysis identifies a subset of downregulated miRNAs in ALS motor neuron progenitors Rizzuti, Mafalda Filosa, Giuseppe Melzi, Valentina Calandriello, Luca Dioni, Laura Bollati, Valentina Bresolin, Nereo Comi, Giacomo Pietro Barabino, Silvia Nizzardo, Monica Corti, Stefania Sci Rep Article Amyotrophic lateral sclerosis (ALS) is a fatal neurological disorder that is characterized by a progressive degeneration of motor neurons (MNs). The pathomechanism underlying the disease is largely unknown, even though increasing evidence suggests that RNA metabolism, including microRNAs (miRNAs) may play an important role. In this study, human ALS induced pluripotent stem cells were differentiated into MN progenitors and their miRNA expression profiles were compared to those of healthy control cells. We identified 15 downregulated miRNAs in patients’ cells. Gene ontology and molecular pathway enrichment analysis indicated that the predicted target genes of the differentially expressed miRNAs were involved in neurodegeneration-related pathways. Among the 15 examined miRNAs, miR-34a and miR504 appeared particularly relevant due to their involvement in the p53 pathway, synaptic vesicle regulation and general involvement in neurodegenerative diseases. Taken together our results demonstrate that the neurodegenerative phenotype in ALS can be associated with a dysregulation of miRNAs involved in the control of disease-relevant genetic pathways, suggesting that targeting entire gene networks can be a potential strategy to treat complex diseases such as ALS. Nature Publishing Group UK 2018-07-04 /pmc/articles/PMC6031650/ /pubmed/29973608 http://dx.doi.org/10.1038/s41598-018-28366-1 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Rizzuti, Mafalda Filosa, Giuseppe Melzi, Valentina Calandriello, Luca Dioni, Laura Bollati, Valentina Bresolin, Nereo Comi, Giacomo Pietro Barabino, Silvia Nizzardo, Monica Corti, Stefania MicroRNA expression analysis identifies a subset of downregulated miRNAs in ALS motor neuron progenitors |
title | MicroRNA expression analysis identifies a subset of downregulated miRNAs in ALS motor neuron progenitors |
title_full | MicroRNA expression analysis identifies a subset of downregulated miRNAs in ALS motor neuron progenitors |
title_fullStr | MicroRNA expression analysis identifies a subset of downregulated miRNAs in ALS motor neuron progenitors |
title_full_unstemmed | MicroRNA expression analysis identifies a subset of downregulated miRNAs in ALS motor neuron progenitors |
title_short | MicroRNA expression analysis identifies a subset of downregulated miRNAs in ALS motor neuron progenitors |
title_sort | microrna expression analysis identifies a subset of downregulated mirnas in als motor neuron progenitors |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6031650/ https://www.ncbi.nlm.nih.gov/pubmed/29973608 http://dx.doi.org/10.1038/s41598-018-28366-1 |
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