EGR1 Overexpression Inhibits the Occurrence of Preeclampsia by Binding to MicroRNA-574 Promoter and Upregulating GAB1.

Early growth response protein 1 (EGR1) is potent in modulating placental trophoblast cell growth and shows a differential expression in preeclampsia (PE). We aimed to identify the downstream mechanism of EGR1 in PE. RT-qPCR showed EGR1 was significantly decreased in PE placenta. Overexpression of EGR1 facilitated the proliferation and invasion of HTR-8/Svneo cells, and reduced the concentration of human chorionic gonadotrophin (HCG) in the supernatant. Bioinformatics prediction, ChIP, and luciferase reporter experiments revealed that EGR1 inhibited miR-574 expression by binding to miR-574 promoter and that miR-574 targeted GAB1. Furthermore, overexpression of miR-574 inhibited the proliferation and invasion of HTR-8/Svneo cells. GAB1 was downregulated in placenta of PE patients, which was positively correlated with EGR1 and negatively correlated with miR-574. Inhibition of GAB1 attenuated the effect of EGR1 overexpression on the proliferation and invasion of HTR-8/Svneo cells. All in all, EGR1 upregulated GAB1 by inhibiting miR-574, thus contributing to trophoblast cell proliferation and invasion.

Effects of forkhead box protein M1 on trophoblast invasion and its role in preeclampsia development.

The present study aimed to investigate the expression of the forkhead box protein M1 (FOXM1) in the placenta of patients with preeclampsia, and its effect on trophoblasts. A total of 28 patients with preeclampsia and 30 patients without preeclampsia (controls) who underwent cesarean section and were admitted to the Affiliated Hospital of Qingdao University between June 2013 and September 2016 were enrolled in the present study. The expression of FOXM1 in placental tissues was examined by reverse transcription-quantitative polymerase chain reaction, western blotting and immunohistochemistry. HTR8/SVneo cells were used to measure the in vitro expression of the vascular endothelial growth factor (VEGF). The results demonstrated that FOXM1 expression was downregulated in the placental tissues of patient with preeclampsia (P<0.05). Following the silencing of FOXM1 expression, the proliferation of HTR8/SVneo cells was suppressed. The results of flow cytometry demonstrated that proportion of HTR8/SVneo cells in the G0/G1 phase and the proportion of apoptotic cells increased. The expression of the apoptosis regulator BCL-2, as well as the expression of VEGF mRNA and protein expression were also downregulated following FOXM1 silencing. FOXM1 may therefore promote the development of preeclampsia via the VEGF signaling pathway.

Screening of differential proteins of placenta tissues in patients with pre-eclampsia by iTRAQ proteomics techniques.

BACKGROUND: Isotopically labeled relative and absolute quantification (iTRAQ) were applied together with liquid chromatogram-tandem mass spectrometry (LC-MS/MS) technique to screen and differentiate normal tissues and differential proteins of placenta tissue in the pre-eclampsia group, and to seek for a pre-eclampsia biomarker. METHODS: Thirty patients with severe pre-eclampsia (pre-eclampsia group) and 30 patients with normal full-term pregnancy (control group), who were admitted by the Obstetrical Department of The Affiliated Hospital of Qingdao University from December 2014 to June 2015, were collected for this study. Part of the placenta tissue was sampled following cesarean section to extract the total protein that was degenerated, reduced and enzymatically hydrolyzed. Following iTRAQ, mass spectroscopy was used for differentiation to obtain differential proteins in the expression. RESULTS: A total of 234 differential proteins were identified. The comparison between the severe pre-eclampsia group and the control group indicated over 1.5-folds of expression abundance difference (upregulation ratio >1.50, or downregulation ratio <0.67). The difference was statistically significant in 24 protein points in total, among which the expression of 14 protein points was upregulated compared with that of the control group, and the expression of 10 protein points was downregulated. CONCLUSIONS: iTRAQ combined with the LC-MS/MS technique can effectively screen differential proteins in placenta tissues of patients with pre-eclampsia.

Genome-wide association study identifies eight new risk loci for polycystic ovary syndrome.

Following a previous genome-wide association study (GWAS 1) including 744 cases and 895 controls, we analyzed genome-wide association data from a new cohort of Han Chinese (GWAS 2) with 1,510 polycystic ovary syndrome (PCOS) cases and 2,016 controls. We followed up significantly associated signals identified in the combined results of GWAS 1 and 2 in a total of 8,226 cases and 7,578 controls. In addition to confirming the three loci we previously reported, we identify eight new PCOS association signals at P < 5 × 10(-8): 9q22.32, 11q22.1, 12q13.2, 12q14.3, 16q12.1, 19p13.3, 20q13.2 and a second independent signal at 2p16.3 (the FSHR gene). These PCOS association signals show evidence of enrichment for candidate genes related to insulin signaling, sexual hormone function and type 2 diabetes (T2D). Other candidate genes were related to calcium signaling and endocytosis. Our findings provide new insight and direction for discovering the biological mechanisms of PCOS.

Genome-wide association study identifies susceptibility loci for polycystic ovary syndrome on chromosome 2p16.3, 2p21 and 9q33.3.

Polycystic ovary syndrome (PCOS) is a common metabolic disorder in women. To identify causative genes, we conducted a genome-wide association study (GWAS) of PCOS in Han Chinese. The discovery set included 744 PCOS cases and 895 controls; subsequent replications involved two independent cohorts (2,840 PCOS cases and 5,012 controls from northern Han Chinese; 498 cases and 780 controls from southern and central Han Chinese). We identified strong evidence of associations between PCOS and three loci: 2p16.3 (rs13405728; combined P-value by meta-analysis P(meta) = 7.55 × 10⁻²¹, odds ratio (OR) 0.71); 2p21 (rs13429458, P(meta) = 1.73 × 10⁻²³, OR 0.67); and 9q33.3 (rs2479106, P(meta) = 8.12 × 10⁻¹9, OR 1.34). These findings provide new insight into the pathogenesis of PCOS. Follow-up studies of the candidate genes in these regions are recommended.