Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Rizzuti, Mafalda, Filosa, Giuseppe, Melzi, Valentina, Calandriello, Luca, Dioni, Laura, Bollati, Valentina, Bresolin, Nereo, Comi, Giacomo Pietro, Barabino, Silvia, Nizzardo, Monica, Corti, Stefania
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
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
_version_ 1783337352255504384
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
work_keys_str_mv AT rizzutimafalda micrornaexpressionanalysisidentifiesasubsetofdownregulatedmirnasinalsmotorneuronprogenitors
AT filosagiuseppe micrornaexpressionanalysisidentifiesasubsetofdownregulatedmirnasinalsmotorneuronprogenitors
AT melzivalentina micrornaexpressionanalysisidentifiesasubsetofdownregulatedmirnasinalsmotorneuronprogenitors
AT calandrielloluca micrornaexpressionanalysisidentifiesasubsetofdownregulatedmirnasinalsmotorneuronprogenitors
AT dionilaura micrornaexpressionanalysisidentifiesasubsetofdownregulatedmirnasinalsmotorneuronprogenitors
AT bollativalentina micrornaexpressionanalysisidentifiesasubsetofdownregulatedmirnasinalsmotorneuronprogenitors
AT bresolinnereo micrornaexpressionanalysisidentifiesasubsetofdownregulatedmirnasinalsmotorneuronprogenitors
AT comigiacomopietro micrornaexpressionanalysisidentifiesasubsetofdownregulatedmirnasinalsmotorneuronprogenitors
AT barabinosilvia micrornaexpressionanalysisidentifiesasubsetofdownregulatedmirnasinalsmotorneuronprogenitors
AT nizzardomonica micrornaexpressionanalysisidentifiesasubsetofdownregulatedmirnasinalsmotorneuronprogenitors
AT cortistefania micrornaexpressionanalysisidentifiesasubsetofdownregulatedmirnasinalsmotorneuronprogenitors