Up-Regulated Expression and Aberrant DNA Methylation of LEP and SH3PXD2A in Pre-Eclampsia

作者：Xiang, Yuqian; Cheng, Yan; Li, Xiaotian; Li, Qiaoli; Xu, Jiawei; Zhang, Junyu; Liu, Yun; Xing, Qinghe; Wang, Lei; He, Lin^*; Zhao, Xinzhi

来源：PLos One, 2013, 8(3): e59753.

DOI：10.1371/journal.pone.0059753

• GENE-EXPRESSION
• PROMOTER HYPOMETHYLATION
• EPIGENETIC MECHANISMS
• PLACENTAL LEPTIN
• BREAST-CANCER
• FOLIC-ACID
• PROTEIN
• INVASION
• HYPERTENSION
• HOMOCYSTEINE

The primary mechanism underlying pre-eclampsia (PE) remains one of the most burning problems in the obstetrics and gynecology. In this study, we performed an expression profiling screen and detected 1312 genes that were differentially expressed (p<0.05 and fold change >1.5) in PE placentas, including LEP and SH3PXD2A. After validating the microarray results, we conducted the quantitative methylation analysis of LEP and SH3PXD2A in preeclamptic (n=16) versus normal placentas (n = 16) Our results showed that many CpG sites close to the transcriptional start site (TSS) of LEP gene were hypomethylated in placentas from pregnancies with PE compared with those of in controls, including the TSS position (p = 0.001), the binding sites of Sp1 (p = 1.57 x 10(-4)), LP1 (p=0.023) and CEBP alpha (p=0.031). Luciferase reporter analysis confirmed the aberrant methylation of LEP promoter and CEBP alpha co-transfection had a role in the regulation of gene expression. Our results indicated the aberrant LEP promoter methylation was involved in the development of PE. We did not find a significant methylation differences between groups in the promoter region of SH3PXD2A, however, a CGI region in the gene body (CGI34) presented a higher methylation in preeclamptic placentas (p = 1.57 x 10(-4)), which might promote the efficiency of gene transcription. We speculated that SH3PXD2A may take part in the pathogenesis of PE through its role in the regulation of trophoblast cell invasion in the period of placenta formation.

• 出版日期2013-3-27
• 单位复旦大学; 上海交通大学