Cargando…

Transcriptome Profiling Uncovers Potential Common Mechanisms in Fetal Trisomies 18 and 21

Human trisomies have recently been investigated using transcriptomics approaches to identify the gene expression (GE) signatures characteristic of each of these specific aneuploidy conditions. We hypothesized that the viability of cells with gross genomic imbalances might be associated with the acti...

Descripción completa

Detalles Bibliográficos
Autores principales: Volk, Marija, Maver, Aleš, Hodžić, Alenka, Lovrečić, Luca, Peterlin, Borut
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Mary Ann Liebert, Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5655413/
https://www.ncbi.nlm.nih.gov/pubmed/29049012
http://dx.doi.org/10.1089/omi.2017.0123
_version_ 1783273530299777024
author Volk, Marija
Maver, Aleš
Hodžić, Alenka
Lovrečić, Luca
Peterlin, Borut
author_facet Volk, Marija
Maver, Aleš
Hodžić, Alenka
Lovrečić, Luca
Peterlin, Borut
author_sort Volk, Marija
collection PubMed
description Human trisomies have recently been investigated using transcriptomics approaches to identify the gene expression (GE) signatures characteristic of each of these specific aneuploidy conditions. We hypothesized that the viability of cells with gross genomic imbalances might be associated with the activation of resilience mechanisms that are common to different trisomies and that are reflected by specific shared GE patterns. We report in this article our microarray GE analyses of amniocytes from fetuses with viable trisomy conditions, trisomy 21 or trisomy 18, to detect such common expression signatures. Comparative analysis of significantly differentially expressed genes in trisomies 18 and 21 revealed six dysregulated genes common to both: OTUD5, ADAMTSL1, TADA2A, PPID, PIAS2, and MAPRE2. These genes are involved in ubiquitination, protein folding, cell proliferation, and apoptosis. Pathway-based enrichment analyses demonstrated that both trisomies showed dysregulation of the PI3K/AKT pathway, cell cycle G2/M DNA damage checkpoint regulation, and cell death and survival, as well as inhibition of the upstream regulator TP53. Our data collectively suggest that trisomies 18 and 21 share common functional GE signatures, implying that common mechanisms of resilience might be activated in aneuploid cells to resist large genomic imbalances. To the best of our knowledge, this is the first study to use global GE profiling data to identify potential common mechanisms in fetal trisomies. Studies of other trisomies using transcriptomics and multiomics approaches might further clarify mechanisms activated in trisomy syndromes.
format Online
Article
Text
id pubmed-5655413
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Mary Ann Liebert, Inc.
record_format MEDLINE/PubMed
spelling pubmed-56554132017-11-02 Transcriptome Profiling Uncovers Potential Common Mechanisms in Fetal Trisomies 18 and 21 Volk, Marija Maver, Aleš Hodžić, Alenka Lovrečić, Luca Peterlin, Borut OMICS Research Articles Human trisomies have recently been investigated using transcriptomics approaches to identify the gene expression (GE) signatures characteristic of each of these specific aneuploidy conditions. We hypothesized that the viability of cells with gross genomic imbalances might be associated with the activation of resilience mechanisms that are common to different trisomies and that are reflected by specific shared GE patterns. We report in this article our microarray GE analyses of amniocytes from fetuses with viable trisomy conditions, trisomy 21 or trisomy 18, to detect such common expression signatures. Comparative analysis of significantly differentially expressed genes in trisomies 18 and 21 revealed six dysregulated genes common to both: OTUD5, ADAMTSL1, TADA2A, PPID, PIAS2, and MAPRE2. These genes are involved in ubiquitination, protein folding, cell proliferation, and apoptosis. Pathway-based enrichment analyses demonstrated that both trisomies showed dysregulation of the PI3K/AKT pathway, cell cycle G2/M DNA damage checkpoint regulation, and cell death and survival, as well as inhibition of the upstream regulator TP53. Our data collectively suggest that trisomies 18 and 21 share common functional GE signatures, implying that common mechanisms of resilience might be activated in aneuploid cells to resist large genomic imbalances. To the best of our knowledge, this is the first study to use global GE profiling data to identify potential common mechanisms in fetal trisomies. Studies of other trisomies using transcriptomics and multiomics approaches might further clarify mechanisms activated in trisomy syndromes. Mary Ann Liebert, Inc. 2017-10-01 2017-10-01 /pmc/articles/PMC5655413/ /pubmed/29049012 http://dx.doi.org/10.1089/omi.2017.0123 Text en © Marija Volk, et al., 2017. Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms of the Creative Commons Attribution Noncommercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
spellingShingle Research Articles
Volk, Marija
Maver, Aleš
Hodžić, Alenka
Lovrečić, Luca
Peterlin, Borut
Transcriptome Profiling Uncovers Potential Common Mechanisms in Fetal Trisomies 18 and 21
title Transcriptome Profiling Uncovers Potential Common Mechanisms in Fetal Trisomies 18 and 21
title_full Transcriptome Profiling Uncovers Potential Common Mechanisms in Fetal Trisomies 18 and 21
title_fullStr Transcriptome Profiling Uncovers Potential Common Mechanisms in Fetal Trisomies 18 and 21
title_full_unstemmed Transcriptome Profiling Uncovers Potential Common Mechanisms in Fetal Trisomies 18 and 21
title_short Transcriptome Profiling Uncovers Potential Common Mechanisms in Fetal Trisomies 18 and 21
title_sort transcriptome profiling uncovers potential common mechanisms in fetal trisomies 18 and 21
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5655413/
https://www.ncbi.nlm.nih.gov/pubmed/29049012
http://dx.doi.org/10.1089/omi.2017.0123
work_keys_str_mv AT volkmarija transcriptomeprofilinguncoverspotentialcommonmechanismsinfetaltrisomies18and21
AT maverales transcriptomeprofilinguncoverspotentialcommonmechanismsinfetaltrisomies18and21
AT hodzicalenka transcriptomeprofilinguncoverspotentialcommonmechanismsinfetaltrisomies18and21
AT lovrecicluca transcriptomeprofilinguncoverspotentialcommonmechanismsinfetaltrisomies18and21
AT peterlinborut transcriptomeprofilinguncoverspotentialcommonmechanismsinfetaltrisomies18and21