Methylated oligonucleotide (MON)-induced promoter hypermethylation is associated with repression of CDH1 expression and contributes to the migration and invasion of human trophoblast cell lines.
Reprod Fertil Dev
; 29(8): 1509-1520, 2017 Aug.
Article
em En
| MEDLINE
| ID: mdl-27439778
ABSTRACT
DNA cytosine-5 methylation plays a vital role in regulating the expression of E-cadherin, which is encoded by the CDH1 gene. In this study, we characterised the DNA methylation and expression pattern of CDH1 in an extravillous trophoblast cell line (HTR-8/SVneo) and two trophoblast cell lines -- JEG-3 and JAR. Promoter hypermethylation with reduced E-cadherin expression in HTR-8/SVneo cells and promoter hypomethylation with increased E-cadherin expression in JEG-3 and JAR cells were observed. Demethylation treatment significantly restored E-cadherin expression, contributing to decreases in the motility and invasiveness of HTR-8/SVneo cells. Sense-methylated oligonucleotides (MONs) labelled with Cy5 and complementary to a region of the human CDH1 promoter were designed, with the cytosines in 5'-cytosine-phosphate-guanine-3' (CpG) dinucleotides being replaced by methylated cytosines. Following MON transfection into JEG-3 cells, the level of CDH1 promoter DNA methylation as well as cell motility and invasiveness were increased and gene expression was significantly repressed. Our results indicate that MON-mediated DNA methylation of the CDH1 promoter and subsequent alterations in gene expression may contribute to trophoblast motility and invasion, suggesting a potential method for controlling the biological function of trophoblasts in vitro through epigenetic modification.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oligonucleotídeos
/
Trofoblastos
/
Caderinas
/
Movimento Celular
/
Regiões Promotoras Genéticas
/
Metilação de DNA
Tipo de estudo:
Risk_factors_studies
Limite:
Female
/
Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article