Dysfunctions of mitochondria in close association with strong perturbation of long noncoding RNAs expression in down syndrome.
Int J Biochem Cell Biol
; 92: 115-120, 2017 11.
Article
em En
| MEDLINE
| ID: mdl-28965985
ABSTRACT
Trisomy 21 is the most common chromosomal disorder and underlies Down syndrome. Epigenetics, such as DNA methylation and post-translational histone modifications, plays a vital role in Down syndrome. However, the functions of epigenetics-related long noncoding RNAs (lncRNAs), found to have an impact on neural diseases such as Alzheimer's disease, remain unknown in Down syndrome. In this study, we analyzed the RNA sequencing data from Down syndrome-induced pluripotent stem cells (iPSCs) and normal iPSCs. A large number of lncRNAs were identified differentially expressed in Down syndrome-iPSCs. Notably, stronger perturbation was shown in the expression of lncRNAs compared to protein coding genes (Kolmogorov-Smirnov test, P<0.05), suggesting that lncRNAs play more important roles in Down syndrome. Through gene set enrichment analysis and bi-clustering, we also found that most of the differential expressed lncRNAs were closely associated with mitochondrial functions (e.g. mitochondrion organization, P=3.21×10-17; mitochondrial ATP synthesis coupled electron transport, P=1.73×10-19 and mitochondrial membrane organization, P=4.04×10-8). PCR-array and qRT-PCR results revealed that almost all genes related to mitochondria were down-regulated in Down syndrome-iPSCs, implying that mitochondria were dysfunctional in Down syndrome (e.g. ATP5B, Fold Change=-8.2317; COX6A1, Fold Change=-12.7788 and SLC25A17, Fold Change=-22.1296). All in all, our study indicated that a stronger perturbation of lncRNAs expression may lead to the dysfunction of mitochondria in Down syndrome.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Síndrome de Down
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Perfilação da Expressão Gênica
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RNA Longo não Codificante
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Mitocôndrias
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Int J Biochem Cell Biol
Assunto da revista:
BIOQUIMICA
Ano de publicação:
2017
Tipo de documento:
Article