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
Xi Lan A , Li-Juan Fu B , Zhuo-Ying Hu C , Qian Feng A , Xue-Qing Liu A , Xue Zhang A , Xue-Mei Chen A , Jun-Lin He A , Ying-Xiong Wang A and Yu-Bin Ding A D
+ Author Affiliations
- Author Affiliations
A Laboratory of Reproductive Biology, School of Public Health and Management, Chongqing Medical University, No.1 Yixueyuan Rd, Chongqing, 400016, P.R. China.
B School of Traditional Chinese Medicine, Chongqing Medical University, No.1 Yixueyuan Rd, Chongqing, 400016, P.R. China.
C Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, No.1 Youyi Rd, Chongqing, 400016, P.R. China.
D Corresponding author. Email: dingyb@gmail.com
Reproduction, Fertility and Development 29(8) 1509-1520 https://doi.org/10.1071/RD16031
Submitted: 12 February 2016 Accepted: 20 June 2016 Published: 21 July 2016
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.
Additional keywords: DNA methylation, E-cadherin, implantation, pregnancy complications.
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