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Mechanistic Insight Into the Regulation of Immune-Related Genes Expression in Autism Spectrum Disorder

Autism spectrum disorder (ASD) is a severe neurodevelopmental disorder featuring impairment in verbal and non-verbal interactions, defects in social interactions, stereotypic behaviors as well as restricted interests. In recent times, the incidence of ASD is growing at a rapid pace. In spite of grea...

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Autores principales: Sabaie, Hani, Dehghani, Hossein, Shiva, Shadi, Asadi, Mohammad Reza, Rezaei, Omidvar, Taheri, Mohammad, Rezazadeh, Maryam
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8568055/
https://www.ncbi.nlm.nih.gov/pubmed/34746237
http://dx.doi.org/10.3389/fmolb.2021.754296
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author Sabaie, Hani
Dehghani, Hossein
Shiva, Shadi
Asadi, Mohammad Reza
Rezaei, Omidvar
Taheri, Mohammad
Rezazadeh, Maryam
author_facet Sabaie, Hani
Dehghani, Hossein
Shiva, Shadi
Asadi, Mohammad Reza
Rezaei, Omidvar
Taheri, Mohammad
Rezazadeh, Maryam
author_sort Sabaie, Hani
collection PubMed
description Autism spectrum disorder (ASD) is a severe neurodevelopmental disorder featuring impairment in verbal and non-verbal interactions, defects in social interactions, stereotypic behaviors as well as restricted interests. In recent times, the incidence of ASD is growing at a rapid pace. In spite of great endeavors devoted to explaining ASD pathophysiology, its precise etiology remains unresolved. ASD pathogenesis is related to different phenomena associated with the immune system; however, the mechanisms behind these immune phenomena as well as the potential contributing genes remain unclear. In the current work, we used a bioinformatics approach to describe the role of long non-coding RNA (lncRNA)-associated competing endogenous RNAs (ceRNAs) in the peripheral blood (PB) samples to figure out the molecular regulatory procedures involved in ASD better. The Gene Expression Omnibus database was used to obtain the PB microarray dataset (GSE89594) from the subjects suffering from ASD and control subjects, containing the data related to both mRNAs and lncRNAs. The list of immune-related genes was obtained from the ImmPort database. In order to determine the immune-related differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs), the limma package of R software was used. A protein-protein interaction network was developed for the immune-related DEmRNAs. By employing the Human MicroRNA Disease Database, DIANA-LncBase, and DIANA-TarBase databases, the RNA interaction pairs were determined. We used the Pearson correlation coefficient to discover the positive correlations between DElncRNAs and DEmRNAs within the ceRNA network. Finally, the lncRNA-associated ceRNA network was created based on DElncRNA-miRNA-DEmRNA interactions and co-expression interactions. In addition, the KEGG enrichment analysis was conducted for immune-related DEmRNAs found within the constructed network. This work found four potential DElncRNA-miRNA-DEmRNA axes in ASD pathogenesis, including, LINC00472/hsa-miR-221-3p/PTPN11, ANP32A-IT1/hsa-miR-182-5p/S100A2, LINC00472/hsa-miR-132-3p/S100A2, and RBM26-AS1/hsa-miR-182-5p/S100A2. According to pathway enrichment analysis, the immune-related DEmRNAs were enriched in the “JAK-STAT signaling pathway” and “Adipocytokine signaling pathway.” An understanding of regulatory mechanisms of ASD-related immune genes would provide novel insights into the molecular mechanisms behind ASD pathogenesis.
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spelling pubmed-85680552021-11-05 Mechanistic Insight Into the Regulation of Immune-Related Genes Expression in Autism Spectrum Disorder Sabaie, Hani Dehghani, Hossein Shiva, Shadi Asadi, Mohammad Reza Rezaei, Omidvar Taheri, Mohammad Rezazadeh, Maryam Front Mol Biosci Molecular Biosciences Autism spectrum disorder (ASD) is a severe neurodevelopmental disorder featuring impairment in verbal and non-verbal interactions, defects in social interactions, stereotypic behaviors as well as restricted interests. In recent times, the incidence of ASD is growing at a rapid pace. In spite of great endeavors devoted to explaining ASD pathophysiology, its precise etiology remains unresolved. ASD pathogenesis is related to different phenomena associated with the immune system; however, the mechanisms behind these immune phenomena as well as the potential contributing genes remain unclear. In the current work, we used a bioinformatics approach to describe the role of long non-coding RNA (lncRNA)-associated competing endogenous RNAs (ceRNAs) in the peripheral blood (PB) samples to figure out the molecular regulatory procedures involved in ASD better. The Gene Expression Omnibus database was used to obtain the PB microarray dataset (GSE89594) from the subjects suffering from ASD and control subjects, containing the data related to both mRNAs and lncRNAs. The list of immune-related genes was obtained from the ImmPort database. In order to determine the immune-related differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs), the limma package of R software was used. A protein-protein interaction network was developed for the immune-related DEmRNAs. By employing the Human MicroRNA Disease Database, DIANA-LncBase, and DIANA-TarBase databases, the RNA interaction pairs were determined. We used the Pearson correlation coefficient to discover the positive correlations between DElncRNAs and DEmRNAs within the ceRNA network. Finally, the lncRNA-associated ceRNA network was created based on DElncRNA-miRNA-DEmRNA interactions and co-expression interactions. In addition, the KEGG enrichment analysis was conducted for immune-related DEmRNAs found within the constructed network. This work found four potential DElncRNA-miRNA-DEmRNA axes in ASD pathogenesis, including, LINC00472/hsa-miR-221-3p/PTPN11, ANP32A-IT1/hsa-miR-182-5p/S100A2, LINC00472/hsa-miR-132-3p/S100A2, and RBM26-AS1/hsa-miR-182-5p/S100A2. According to pathway enrichment analysis, the immune-related DEmRNAs were enriched in the “JAK-STAT signaling pathway” and “Adipocytokine signaling pathway.” An understanding of regulatory mechanisms of ASD-related immune genes would provide novel insights into the molecular mechanisms behind ASD pathogenesis. Frontiers Media S.A. 2021-10-21 /pmc/articles/PMC8568055/ /pubmed/34746237 http://dx.doi.org/10.3389/fmolb.2021.754296 Text en Copyright © 2021 Sabaie, Dehghani, Shiva, Asadi, Rezaei, Taheri and Rezazadeh. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Biosciences
Sabaie, Hani
Dehghani, Hossein
Shiva, Shadi
Asadi, Mohammad Reza
Rezaei, Omidvar
Taheri, Mohammad
Rezazadeh, Maryam
Mechanistic Insight Into the Regulation of Immune-Related Genes Expression in Autism Spectrum Disorder
title Mechanistic Insight Into the Regulation of Immune-Related Genes Expression in Autism Spectrum Disorder
title_full Mechanistic Insight Into the Regulation of Immune-Related Genes Expression in Autism Spectrum Disorder
title_fullStr Mechanistic Insight Into the Regulation of Immune-Related Genes Expression in Autism Spectrum Disorder
title_full_unstemmed Mechanistic Insight Into the Regulation of Immune-Related Genes Expression in Autism Spectrum Disorder
title_short Mechanistic Insight Into the Regulation of Immune-Related Genes Expression in Autism Spectrum Disorder
title_sort mechanistic insight into the regulation of immune-related genes expression in autism spectrum disorder
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8568055/
https://www.ncbi.nlm.nih.gov/pubmed/34746237
http://dx.doi.org/10.3389/fmolb.2021.754296
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