Effect of STAT3 mediated epigenetic regulation in pre-eclampsia: an analysis of trial data

X.-L. Zhang, J. Pan, G. Wang, H. Li, J.-L. Wang, X.-M. Jiang, X.-Y. Zhao

Department of Obstetrics and Gynecology, Affiliated Huadu Hospital, Southern Medical University, Guangzhou, China. ace0829@sina.com

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• Obstetrics

OBJECTIVE: To study the role of the PI3K-AKT/mTor signalling pathway, mediated by the STAT3 gene, in the epigenetic pathogenesis of pre-eclampsia.

MATERIALS AND METHODS: HTR8/Svneo, JEG-3, JAR, and Bewo trophoblast cell lines were divided into a PE group and a control group. STAT3 gene overexpression and interference silencing, immunofluorescence, Real Time-PCR and Western blot, GST-pull down, CHIP, Dual-Luciferase reporter gene test, Rescue experiment, LC-MS/MS analysis. Methods and materials also comprised CCK-8, transwell invasion, MSP and BSP, flow cytometry and wound-healing assay.

RESULTS: Compared with the control group, the expression of DNMT1 mRNA and protein was increased, while the expression of STAT3, PTEN, TSC2 mRNA and protein was decreased. There was improvement after 5-Aza-2’-deoxycytidine (5-AZA-DC) intervention.GST-pull down confirms that STAT3 interacts with PTEN and TSC2. CHIP verifies that STAT3 binds directly to PTEN, and double luciferase reporter experiments verify that STAT3 regulates PTEN promoter activity. STAT3 expression of PTEN is, meanwhile, saved by knock down of PTEN in HTR8/SVneo cells. LC-MS/MS analysis showed upregulation of STAT3, PTEN, TSC2 and TSC2. MSP and BSP analysis screened out the significant difference genes of STAT3, PTEN and TSC2. Following 5-AZA-DC intervention, apoptosis downregulation, invasion upregulation and cell-proliferation upregulation were evinced.

CONCLUSIONS: Trophoblast STAT3 was an important gene mediating the pathogenesis of pre-eclampsia induced by the PI3K-AKT/mTor signal axis. In the context of epigenetic therapy for pre-eclampsia, STAT3 may be deployed as a potential target.

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