Elevated MicroRNA 183 Impairs Trophoblast Migration and Invasiveness by Downregulating FOXP1 Expression and Elevating GNG7 Expression during Preeclampsia

ABSTRACT

Preeclampsia (PE) is a hypertensive disorder of uncertain etiology that is the leading cause of maternal and fetal morbidity or mortality. The dysregulation of microRNAs (miRNAs) has been highlighted as a potential factor involved in the development of PE. Therefore, our study investigated a novel miRNA, miRNA 183 (miR-183), and its underlying association with PE. Expression of miR-183, forkhead box P1 (FOXP1), and G protein subunit gamma 7 (GNG7) in placental tissues of patients with PE was determined. Gain- and loss-of-function experiments were conducted to explore modulatory effects of miR-183, FOXP1, and GNG7 on the viability, invasion, and angiogenesis of trophoblast cells in PE. Finally, we undertook in vivo studies to explore effects of FOXP1 in the PE model. The results revealed suppressed expression of FOXP1 and significant elevations in miR-183 and GNG7 expression in placental tissues of PE patients. FOXP1 was observed to promote proliferation, invasion, and angiogenesis in human chorionic trophoblastic cells. miR-183 resulted in depletion of FOXP1 expression, while FOXP1 was capable of restraining GNG7 expression and promoting the mTOR pathway. The findings confirmed the effects of FOXP1 on PE. In conclusion, miR-183 exhibits an inhibitory role in PE through suppression of FOXP1 and upregulation of GNG7.

KEYWORDS:

• Preeclampsia
• microRNA-183
• forkhead box P1
• G protein subunit gamma 7
• mechanistic target of rapamycin kinase

ACKNOWLEDGMENTS

We acknowledge the helpful comments on this paper received from the reviewers.

Ling Yu and Weisi Lai designed the study. Ling Yu and Weisi Lai collated the data, carried out data analyses, and produced the initial draft of the manuscript. Ling Yu contributed to drafting the manuscript. Both of us read and approved the final submitted manuscript.

We declare no conflicts of interest.