| Title: |
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. |
| Authors: |
Xi Lan1, Li-Juan Fu2, Zhuo-Ying Hu3, Qian Feng1, Xue-Qing Liu1, Xue Zhang1, Xue-Mei Chen1, Jun-Lin He1, Ying-Xiong Wang1, Yu-Bin Ding1 dingyb@gmail.com |
| Source: |
Reproduction, Fertility & Development. 2017, Vol. 29 Issue 8, p1509-1520. 13p. |
| Subject Terms: |
*OLIGONUCLEOTIDES, *PROMOTERS (Genetics), *DNA methylation, *CADHERINS, *GENE expression |
| Abstract: |
DNAcytosine-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 CDH1promoter were designed, with the cytosines in 50-cytosine-phosphate-guanine-30 (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. [ABSTRACT FROM AUTHOR] |
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