Identification of miRNAs differentially expressed in human epilepsy with or without granule cell pathology.

The microRNAs (miRNAs) are small size non-coding RNAs that regulate expression of target mRNAs at post-transcriptional level. miRNAs differentially expressed under pathological conditions may help identifying mechanisms underlying the disease and may represent biomarkers with prognostic value. Howev...

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Autores principales: Silvia Zucchini, Gianluca Marucci, Beatrice Paradiso, Giovanni Lanza, Paolo Roncon, Pierangelo Cifelli, Manuela Ferracin, Marco Giulioni, Roberto Michelucci, Guido Rubboli, Michele Simonato
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Publicado: Public Library of Science (PLoS) 2014
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Acceso en línea:https://doaj.org/article/a1b8086a0c51450186534d9f2298521f
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spelling oai:doaj.org-article:a1b8086a0c51450186534d9f2298521f2021-11-25T06:03:34ZIdentification of miRNAs differentially expressed in human epilepsy with or without granule cell pathology.1932-620310.1371/journal.pone.0105521https://doaj.org/article/a1b8086a0c51450186534d9f2298521f2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25148080/?tool=EBIhttps://doaj.org/toc/1932-6203The microRNAs (miRNAs) are small size non-coding RNAs that regulate expression of target mRNAs at post-transcriptional level. miRNAs differentially expressed under pathological conditions may help identifying mechanisms underlying the disease and may represent biomarkers with prognostic value. However, this kind of studies are difficult in the brain because of the cellular heterogeneity of the tissue and of the limited access to fresh tissue. Here, we focused on a pathology affecting specific cells in a subpopulation of epileptic brains (hippocampal granule cells), an approach that bypasses the above problems. All patients underwent surgery for intractable temporal lobe epilepsy and had hippocampal sclerosis associated with no granule cell pathology in half of the cases and with type-2 granule cell pathology (granule cell layer dispersion or bilamination) in the other half. The expression of more than 1000 miRNAs was examined in the laser-microdissected dentate granule cell layer. Twelve miRNAs were differentially expressed in the two groups. One of these, miR487a, was confirmed to be expressed at highly differential levels in an extended cohort of patients, using RT-qPCR. Bioinformatics searches and RT-qPCR verification identified ANTXR1 as a possible target of miR487a. ANTXR1 may be directly implicated in granule cell dispersion because it is an adhesion molecule that favors cell spreading. Thus, miR487a could be the first identified element of a miRNA signature that may be useful for prognostic evaluation of post-surgical epilepsy and may drive mechanistic studies leading to the identification of therapeutic targets.Silvia ZucchiniGianluca MarucciBeatrice ParadisoGiovanni LanzaPaolo RonconPierangelo CifelliManuela FerracinMarco GiulioniRoberto MichelucciGuido RubboliMichele SimonatoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 8, p e105521 (2014)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Silvia Zucchini
Gianluca Marucci
Beatrice Paradiso
Giovanni Lanza
Paolo Roncon
Pierangelo Cifelli
Manuela Ferracin
Marco Giulioni
Roberto Michelucci
Guido Rubboli
Michele Simonato
Identification of miRNAs differentially expressed in human epilepsy with or without granule cell pathology.
description The microRNAs (miRNAs) are small size non-coding RNAs that regulate expression of target mRNAs at post-transcriptional level. miRNAs differentially expressed under pathological conditions may help identifying mechanisms underlying the disease and may represent biomarkers with prognostic value. However, this kind of studies are difficult in the brain because of the cellular heterogeneity of the tissue and of the limited access to fresh tissue. Here, we focused on a pathology affecting specific cells in a subpopulation of epileptic brains (hippocampal granule cells), an approach that bypasses the above problems. All patients underwent surgery for intractable temporal lobe epilepsy and had hippocampal sclerosis associated with no granule cell pathology in half of the cases and with type-2 granule cell pathology (granule cell layer dispersion or bilamination) in the other half. The expression of more than 1000 miRNAs was examined in the laser-microdissected dentate granule cell layer. Twelve miRNAs were differentially expressed in the two groups. One of these, miR487a, was confirmed to be expressed at highly differential levels in an extended cohort of patients, using RT-qPCR. Bioinformatics searches and RT-qPCR verification identified ANTXR1 as a possible target of miR487a. ANTXR1 may be directly implicated in granule cell dispersion because it is an adhesion molecule that favors cell spreading. Thus, miR487a could be the first identified element of a miRNA signature that may be useful for prognostic evaluation of post-surgical epilepsy and may drive mechanistic studies leading to the identification of therapeutic targets.
format article
author Silvia Zucchini
Gianluca Marucci
Beatrice Paradiso
Giovanni Lanza
Paolo Roncon
Pierangelo Cifelli
Manuela Ferracin
Marco Giulioni
Roberto Michelucci
Guido Rubboli
Michele Simonato
author_facet Silvia Zucchini
Gianluca Marucci
Beatrice Paradiso
Giovanni Lanza
Paolo Roncon
Pierangelo Cifelli
Manuela Ferracin
Marco Giulioni
Roberto Michelucci
Guido Rubboli
Michele Simonato
author_sort Silvia Zucchini
title Identification of miRNAs differentially expressed in human epilepsy with or without granule cell pathology.
title_short Identification of miRNAs differentially expressed in human epilepsy with or without granule cell pathology.
title_full Identification of miRNAs differentially expressed in human epilepsy with or without granule cell pathology.
title_fullStr Identification of miRNAs differentially expressed in human epilepsy with or without granule cell pathology.
title_full_unstemmed Identification of miRNAs differentially expressed in human epilepsy with or without granule cell pathology.
title_sort identification of mirnas differentially expressed in human epilepsy with or without granule cell pathology.
publisher Public Library of Science (PLoS)
publishDate 2014
url https://doaj.org/article/a1b8086a0c51450186534d9f2298521f
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