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Identification and Analysis of BCAS4/hsa-miR-185-5p/SHISA7 Competing Endogenous RNA Axis in Late-Onset Alzheimer’s Disease Using Bioinformatic and Experimental Approaches

Alzheimer’s disease (AD) is a heterogeneous degenerative brain disorder with a rising prevalence worldwide. SHISA7 (CKAMP59) has emerged as one of the most intriguing new members of the SHISA family, in that, unlike other CKAMP counterparts, it exhibits a direct function in inhibitory synaptic GABAA...

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Autores principales: Sabaie, Hani, Talebi, Mahnaz, Gharesouarn, Jalal, Asadi, Mohammad Reza, Jalaiei, Abbas, Arsang-Jang, Shahram, Hussen, Bashdar Mahmud, Taheri, Mohammad, Jalili Khoshnoud, Reza, Rezazadeh, Maryam
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8899724/
https://www.ncbi.nlm.nih.gov/pubmed/35264942
http://dx.doi.org/10.3389/fnagi.2022.812169
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author Sabaie, Hani
Talebi, Mahnaz
Gharesouarn, Jalal
Asadi, Mohammad Reza
Jalaiei, Abbas
Arsang-Jang, Shahram
Hussen, Bashdar Mahmud
Taheri, Mohammad
Jalili Khoshnoud, Reza
Rezazadeh, Maryam
author_facet Sabaie, Hani
Talebi, Mahnaz
Gharesouarn, Jalal
Asadi, Mohammad Reza
Jalaiei, Abbas
Arsang-Jang, Shahram
Hussen, Bashdar Mahmud
Taheri, Mohammad
Jalili Khoshnoud, Reza
Rezazadeh, Maryam
author_sort Sabaie, Hani
collection PubMed
description Alzheimer’s disease (AD) is a heterogeneous degenerative brain disorder with a rising prevalence worldwide. SHISA7 (CKAMP59) has emerged as one of the most intriguing new members of the SHISA family, in that, unlike other CKAMP counterparts, it exhibits a direct function in inhibitory synaptic GABAAR regulation. We used bioinformatics and experimental methods in this research to explore competing endogenous RNA (ceRNA) regulation of BCAS4 and SHISA7 in tau pathogenesis and their capacity as peripheral biomarkers linked to an abnormal inflammatory response in AD. The Gene Expression Omnibus database included two microarray datasets, including information on mRNAs (GSE106241) and miRNAs (GSE157239) from individuals with AD with different degrees of AD-associated neurofibrillary pathology in the temporal cortex (TC) tissue specimens and corresponding controls were downloaded from the Gene Expression Omnibus database. The limma package in the R software was used to identify differently expressed mRNAs (DEmRNAs) and miRNAs (DEmiRNAs) associated with AD-related neurofibrillary pathology. Additionally, we used the quantitative polymerase chain reaction technique to examine the expression of the BCAS4/hsa-miR-185-5p/SHISA7 ceRNA axis in the peripheral blood (PB) of fifty AD patients and fifty control subjects. BCAS4 was shown to act as a ceRNA to control the SHISA7 expression throughout AD-associated neurofibrillary pathology in TC tissue specimens by sponging hsa-miR-185-5p, based on our bioinformatics study. Furthermore, in PB specimens from individuals suffering from AD and normal controls, we found no substantial differences in BCAS4 expression patterns. SHISA7 expression in AD patients’ PB was found to be reduced, as was the case in the TC. On the other hand, we discovered reduced amounts of hsa-miR-185-5p in AD patients’ PB samples compared to control subjects, unlike in TC tissue, where it had been demonstrated to be overexpressed. BCAS4 and SHISA7 expression levels showed a strong positive correlation, suggesting the presence of an interconnected network, most likely as a result of ceRNA regulation among PB specimens. The present study is the first evidence to highlight the expression of the BCAS4/miR-185-5p/SHISA7 ceRNA axis in the brain and PB of AD patients, and offers a new viewpoint on molecular processes underlying AD pathogenic mechanisms.
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spelling pubmed-88997242022-03-08 Identification and Analysis of BCAS4/hsa-miR-185-5p/SHISA7 Competing Endogenous RNA Axis in Late-Onset Alzheimer’s Disease Using Bioinformatic and Experimental Approaches Sabaie, Hani Talebi, Mahnaz Gharesouarn, Jalal Asadi, Mohammad Reza Jalaiei, Abbas Arsang-Jang, Shahram Hussen, Bashdar Mahmud Taheri, Mohammad Jalili Khoshnoud, Reza Rezazadeh, Maryam Front Aging Neurosci Neuroscience Alzheimer’s disease (AD) is a heterogeneous degenerative brain disorder with a rising prevalence worldwide. SHISA7 (CKAMP59) has emerged as one of the most intriguing new members of the SHISA family, in that, unlike other CKAMP counterparts, it exhibits a direct function in inhibitory synaptic GABAAR regulation. We used bioinformatics and experimental methods in this research to explore competing endogenous RNA (ceRNA) regulation of BCAS4 and SHISA7 in tau pathogenesis and their capacity as peripheral biomarkers linked to an abnormal inflammatory response in AD. The Gene Expression Omnibus database included two microarray datasets, including information on mRNAs (GSE106241) and miRNAs (GSE157239) from individuals with AD with different degrees of AD-associated neurofibrillary pathology in the temporal cortex (TC) tissue specimens and corresponding controls were downloaded from the Gene Expression Omnibus database. The limma package in the R software was used to identify differently expressed mRNAs (DEmRNAs) and miRNAs (DEmiRNAs) associated with AD-related neurofibrillary pathology. Additionally, we used the quantitative polymerase chain reaction technique to examine the expression of the BCAS4/hsa-miR-185-5p/SHISA7 ceRNA axis in the peripheral blood (PB) of fifty AD patients and fifty control subjects. BCAS4 was shown to act as a ceRNA to control the SHISA7 expression throughout AD-associated neurofibrillary pathology in TC tissue specimens by sponging hsa-miR-185-5p, based on our bioinformatics study. Furthermore, in PB specimens from individuals suffering from AD and normal controls, we found no substantial differences in BCAS4 expression patterns. SHISA7 expression in AD patients’ PB was found to be reduced, as was the case in the TC. On the other hand, we discovered reduced amounts of hsa-miR-185-5p in AD patients’ PB samples compared to control subjects, unlike in TC tissue, where it had been demonstrated to be overexpressed. BCAS4 and SHISA7 expression levels showed a strong positive correlation, suggesting the presence of an interconnected network, most likely as a result of ceRNA regulation among PB specimens. The present study is the first evidence to highlight the expression of the BCAS4/miR-185-5p/SHISA7 ceRNA axis in the brain and PB of AD patients, and offers a new viewpoint on molecular processes underlying AD pathogenic mechanisms. Frontiers Media S.A. 2022-02-21 /pmc/articles/PMC8899724/ /pubmed/35264942 http://dx.doi.org/10.3389/fnagi.2022.812169 Text en Copyright © 2022 Sabaie, Talebi, Gharesouarn, Asadi, Jalaiei, Arsang-Jang, Hussen, Taheri, Jalili Khoshnoud 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 Neuroscience
Sabaie, Hani
Talebi, Mahnaz
Gharesouarn, Jalal
Asadi, Mohammad Reza
Jalaiei, Abbas
Arsang-Jang, Shahram
Hussen, Bashdar Mahmud
Taheri, Mohammad
Jalili Khoshnoud, Reza
Rezazadeh, Maryam
Identification and Analysis of BCAS4/hsa-miR-185-5p/SHISA7 Competing Endogenous RNA Axis in Late-Onset Alzheimer’s Disease Using Bioinformatic and Experimental Approaches
title Identification and Analysis of BCAS4/hsa-miR-185-5p/SHISA7 Competing Endogenous RNA Axis in Late-Onset Alzheimer’s Disease Using Bioinformatic and Experimental Approaches
title_full Identification and Analysis of BCAS4/hsa-miR-185-5p/SHISA7 Competing Endogenous RNA Axis in Late-Onset Alzheimer’s Disease Using Bioinformatic and Experimental Approaches
title_fullStr Identification and Analysis of BCAS4/hsa-miR-185-5p/SHISA7 Competing Endogenous RNA Axis in Late-Onset Alzheimer’s Disease Using Bioinformatic and Experimental Approaches
title_full_unstemmed Identification and Analysis of BCAS4/hsa-miR-185-5p/SHISA7 Competing Endogenous RNA Axis in Late-Onset Alzheimer’s Disease Using Bioinformatic and Experimental Approaches
title_short Identification and Analysis of BCAS4/hsa-miR-185-5p/SHISA7 Competing Endogenous RNA Axis in Late-Onset Alzheimer’s Disease Using Bioinformatic and Experimental Approaches
title_sort identification and analysis of bcas4/hsa-mir-185-5p/shisa7 competing endogenous rna axis in late-onset alzheimer’s disease using bioinformatic and experimental approaches
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8899724/
https://www.ncbi.nlm.nih.gov/pubmed/35264942
http://dx.doi.org/10.3389/fnagi.2022.812169
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