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Increased Serum Levels of miR-125b and miR-132 in Fragile X Syndrome: A Preliminary Study

BACKGROUND AND OBJECTIVES: Fragile X syndrome (FXS) is a neurodevelopmental disorder, identified as the most common cause of hereditary intellectual disability and monogenic cause of autism spectrum disorders (ASDs), caused by the loss of fragile X mental retardation protein (FMRP). FMRP is an RNA-b...

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Autores principales: Couto, Rowena Rubim, Kubaski, Francyne, Siebert, Marina, Félix, Têmis Maria, Brusius-Facchin, Ana Carolina, Leistner-Segal, Sandra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wolters Kluwer 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9608387/
https://www.ncbi.nlm.nih.gov/pubmed/36313066
http://dx.doi.org/10.1212/NXG.0000000000200024
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author Couto, Rowena Rubim
Kubaski, Francyne
Siebert, Marina
Félix, Têmis Maria
Brusius-Facchin, Ana Carolina
Leistner-Segal, Sandra
author_facet Couto, Rowena Rubim
Kubaski, Francyne
Siebert, Marina
Félix, Têmis Maria
Brusius-Facchin, Ana Carolina
Leistner-Segal, Sandra
author_sort Couto, Rowena Rubim
collection PubMed
description BACKGROUND AND OBJECTIVES: Fragile X syndrome (FXS) is a neurodevelopmental disorder, identified as the most common cause of hereditary intellectual disability and monogenic cause of autism spectrum disorders (ASDs), caused by the loss of fragile X mental retardation protein (FMRP). FMRP is an RNA-binding protein, a regulator of translation that plays an important role in neurodevelopment, and its loss causes cognitive and behavioral deficits. MicroRNAs (miRNAs) are small molecules that regulate gene expression in diverse biological processes. Previous studies found that the interaction of FMRP with miR-125b and miR-132 regulates the maturation and synaptic plasticity in animal models and miRNA dysregulation plays a role in the pathophysiology of FXS. The present study aimed to analyze the expression of miR-125b-5p and miR-132-3p in the serum of patients with FXS. METHODS: The expressions of circulating miRNAs were studied in the serum of 10 patients with FXS and 20 controls using the real-time quantitative retrotranscribed method analyzed by relative quantification. Receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) were generated to assess the diagnostic values of the miRNAs. RESULTS: We found that both miR-125b and miR-132 were increased in the serum of patients with FXS compared with controls and likely involved with FMRP loss. The AUC (95% confidence interval) of miR-125b and miR-132 was 0.94 (0.86–1.0) and 0.89 (0.77–1.0), respectively. Databases allowed for the identification of possible target genes for miR-125b and miR-132, whose products play an important role in the homeostasis of the nervous system. DISCUSSION: Our results indicate that serum miR-125b and miR-132 may serve as potential biomarkers for FXS. The increased expression of circulating miR-125b and miR-132 seems to be associated with the genotype of FXS. Predicted gene targets of the differentially regulated miRNAs are involved in cognitive performance and ASD phenotype. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that miR-125b and miR-132 distinguish men with FXS from normal controls.
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spelling pubmed-96083872022-10-27 Increased Serum Levels of miR-125b and miR-132 in Fragile X Syndrome: A Preliminary Study Couto, Rowena Rubim Kubaski, Francyne Siebert, Marina Félix, Têmis Maria Brusius-Facchin, Ana Carolina Leistner-Segal, Sandra Neurol Genet Research Article BACKGROUND AND OBJECTIVES: Fragile X syndrome (FXS) is a neurodevelopmental disorder, identified as the most common cause of hereditary intellectual disability and monogenic cause of autism spectrum disorders (ASDs), caused by the loss of fragile X mental retardation protein (FMRP). FMRP is an RNA-binding protein, a regulator of translation that plays an important role in neurodevelopment, and its loss causes cognitive and behavioral deficits. MicroRNAs (miRNAs) are small molecules that regulate gene expression in diverse biological processes. Previous studies found that the interaction of FMRP with miR-125b and miR-132 regulates the maturation and synaptic plasticity in animal models and miRNA dysregulation plays a role in the pathophysiology of FXS. The present study aimed to analyze the expression of miR-125b-5p and miR-132-3p in the serum of patients with FXS. METHODS: The expressions of circulating miRNAs were studied in the serum of 10 patients with FXS and 20 controls using the real-time quantitative retrotranscribed method analyzed by relative quantification. Receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) were generated to assess the diagnostic values of the miRNAs. RESULTS: We found that both miR-125b and miR-132 were increased in the serum of patients with FXS compared with controls and likely involved with FMRP loss. The AUC (95% confidence interval) of miR-125b and miR-132 was 0.94 (0.86–1.0) and 0.89 (0.77–1.0), respectively. Databases allowed for the identification of possible target genes for miR-125b and miR-132, whose products play an important role in the homeostasis of the nervous system. DISCUSSION: Our results indicate that serum miR-125b and miR-132 may serve as potential biomarkers for FXS. The increased expression of circulating miR-125b and miR-132 seems to be associated with the genotype of FXS. Predicted gene targets of the differentially regulated miRNAs are involved in cognitive performance and ASD phenotype. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that miR-125b and miR-132 distinguish men with FXS from normal controls. Wolters Kluwer 2022-10-26 /pmc/articles/PMC9608387/ /pubmed/36313066 http://dx.doi.org/10.1212/NXG.0000000000200024 Text en Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
spellingShingle Research Article
Couto, Rowena Rubim
Kubaski, Francyne
Siebert, Marina
Félix, Têmis Maria
Brusius-Facchin, Ana Carolina
Leistner-Segal, Sandra
Increased Serum Levels of miR-125b and miR-132 in Fragile X Syndrome: A Preliminary Study
title Increased Serum Levels of miR-125b and miR-132 in Fragile X Syndrome: A Preliminary Study
title_full Increased Serum Levels of miR-125b and miR-132 in Fragile X Syndrome: A Preliminary Study
title_fullStr Increased Serum Levels of miR-125b and miR-132 in Fragile X Syndrome: A Preliminary Study
title_full_unstemmed Increased Serum Levels of miR-125b and miR-132 in Fragile X Syndrome: A Preliminary Study
title_short Increased Serum Levels of miR-125b and miR-132 in Fragile X Syndrome: A Preliminary Study
title_sort increased serum levels of mir-125b and mir-132 in fragile x syndrome: a preliminary study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9608387/
https://www.ncbi.nlm.nih.gov/pubmed/36313066
http://dx.doi.org/10.1212/NXG.0000000000200024
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