Differential Expression and miRNA–Gene Interactions in Early and Late Mild Cognitive Impairment

Mild cognitive impairment (MCI) and Alzheimer’s Disease (AD) are complex diseases with their molecular architecture not elucidated. <i>APOE</i>, Amyloid Beta Precursor Protein (<i>APP</i>), and Presenilin-1 (<i>PSEN1</i>) are well-known genes associated with both...

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Main Authors: Leonardo Miranda Brito, Ândrea Ribeiro-dos-Santos, Amanda Ferreira Vidal, Gilderlanio Santana de Araújo
Format: Article
Language:English
Published: MDPI AG 2020-08-01
Series:Biology
Subjects:
Online Access:https://www.mdpi.com/2079-7737/9/9/251
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author Leonardo Miranda Brito
Ândrea Ribeiro-dos-Santos
Amanda Ferreira Vidal
Gilderlanio Santana de Araújo
author_facet Leonardo Miranda Brito
Ândrea Ribeiro-dos-Santos
Amanda Ferreira Vidal
Gilderlanio Santana de Araújo
author_sort Leonardo Miranda Brito
collection DOAJ
description Mild cognitive impairment (MCI) and Alzheimer’s Disease (AD) are complex diseases with their molecular architecture not elucidated. <i>APOE</i>, Amyloid Beta Precursor Protein (<i>APP</i>), and Presenilin-1 (<i>PSEN1</i>) are well-known genes associated with both MCI and AD. Recently, epigenetic alterations and dysregulated regulatory elements, such as microRNAs (miRNAs), have been reported associated with neurodegeneration. In this study, differential expression analysis (DEA) was performed for genes and miRNAs based on microarray and RNA-Seq data. Global gene profile of healthy individuals, early and late mild cognitive impairment (EMCI and LMCI, respectively), and AD was obtained from ADNI Cohort. miRNA global profile of healthy individuals and AD patients was extracted from public RNA-Seq data. DEA performed with <i>limma</i> package on ADNI Cohort data highlighted eight differential expressed (DE) genes (<i>AGER</i>, <i>LINC00483</i>, <i>MMP19</i>, <i>CATSPER1</i>, <i>ARFGAP1</i>, <i>GPER1</i>, <i>PHLPP2</i>, <i>TRPM2</i>) (false discovery rate (FDR) <i>p</i>-value < 0.05) between EMCI and LMCI patients. Previous molecular studies showed associations between these genes with dementia and neurological-related pathways. Five dysregulated miRNAs were identified by DEA performed with RNA-Seq data and <i>edgeR</i> (FDR <i>p</i>-value < 0.002). All reported miRNAs in AD interact with the aforementioned genes. Our integrative transcriptomic analysis was able to identify a set of miRNA–gene interactions that may be involved in cognitive and neurodegeneration processes.
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spelling doaj.art-3b108baefa8341e1956aa59fc85493af2023-11-20T11:41:05ZengMDPI AGBiology2079-77372020-08-019925110.3390/biology9090251Differential Expression and miRNA–Gene Interactions in Early and Late Mild Cognitive ImpairmentLeonardo Miranda Brito0Ândrea Ribeiro-dos-Santos1Amanda Ferreira Vidal2Gilderlanio Santana de Araújo3Laboratório de Genética Humana e Médica, Instituto de Ciêncas Biológicas, Universidade Federal do Pará, Belém 66075-110, BrazilLaboratório de Genética Humana e Médica, Instituto de Ciêncas Biológicas, Universidade Federal do Pará, Belém 66075-110, BrazilLaboratório de Genética Humana e Médica, Instituto de Ciêncas Biológicas, Universidade Federal do Pará, Belém 66075-110, BrazilLaboratório de Genética Humana e Médica, Instituto de Ciêncas Biológicas, Universidade Federal do Pará, Belém 66075-110, BrazilMild cognitive impairment (MCI) and Alzheimer’s Disease (AD) are complex diseases with their molecular architecture not elucidated. <i>APOE</i>, Amyloid Beta Precursor Protein (<i>APP</i>), and Presenilin-1 (<i>PSEN1</i>) are well-known genes associated with both MCI and AD. Recently, epigenetic alterations and dysregulated regulatory elements, such as microRNAs (miRNAs), have been reported associated with neurodegeneration. In this study, differential expression analysis (DEA) was performed for genes and miRNAs based on microarray and RNA-Seq data. Global gene profile of healthy individuals, early and late mild cognitive impairment (EMCI and LMCI, respectively), and AD was obtained from ADNI Cohort. miRNA global profile of healthy individuals and AD patients was extracted from public RNA-Seq data. DEA performed with <i>limma</i> package on ADNI Cohort data highlighted eight differential expressed (DE) genes (<i>AGER</i>, <i>LINC00483</i>, <i>MMP19</i>, <i>CATSPER1</i>, <i>ARFGAP1</i>, <i>GPER1</i>, <i>PHLPP2</i>, <i>TRPM2</i>) (false discovery rate (FDR) <i>p</i>-value < 0.05) between EMCI and LMCI patients. Previous molecular studies showed associations between these genes with dementia and neurological-related pathways. Five dysregulated miRNAs were identified by DEA performed with RNA-Seq data and <i>edgeR</i> (FDR <i>p</i>-value < 0.002). All reported miRNAs in AD interact with the aforementioned genes. Our integrative transcriptomic analysis was able to identify a set of miRNA–gene interactions that may be involved in cognitive and neurodegeneration processes.https://www.mdpi.com/2079-7737/9/9/251mild cognitive impairmentAlzheimer’s DiseasegenesmiRNAsregulatory interactions
spellingShingle Leonardo Miranda Brito
Ândrea Ribeiro-dos-Santos
Amanda Ferreira Vidal
Gilderlanio Santana de Araújo
Differential Expression and miRNA–Gene Interactions in Early and Late Mild Cognitive Impairment
Biology
mild cognitive impairment
Alzheimer’s Disease
genes
miRNAs
regulatory interactions
title Differential Expression and miRNA–Gene Interactions in Early and Late Mild Cognitive Impairment
title_full Differential Expression and miRNA–Gene Interactions in Early and Late Mild Cognitive Impairment
title_fullStr Differential Expression and miRNA–Gene Interactions in Early and Late Mild Cognitive Impairment
title_full_unstemmed Differential Expression and miRNA–Gene Interactions in Early and Late Mild Cognitive Impairment
title_short Differential Expression and miRNA–Gene Interactions in Early and Late Mild Cognitive Impairment
title_sort differential expression and mirna gene interactions in early and late mild cognitive impairment
topic mild cognitive impairment
Alzheimer’s Disease
genes
miRNAs
regulatory interactions
url https://www.mdpi.com/2079-7737/9/9/251
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